Food Combination and Alzheimer Disease Risk A Protective Diet
Yian Gu, PhD; Jeri W. Nieves, PhD; Yaakov Stern, PhD; Jose A. Luchsinger, MD, MPH; Nikolaos Scarmeas, MD, MS
Arch Neurol. 2010;67(6):(doi:10.1001/archneurol.2010.84).
ABSTRACT
Objective To assess the association between food combination and Alzheimer disease (AD) risk. Because foods are not consumed in isolation, dietary pattern (DP) analysis of food combination, taking into account the interactions among food components, may offer methodological advantages.
Design Prospective cohort study.
Setting Northern Manhattan, New York, New York.
Patients or Other Participants Two thousand one hundred forty-eight community-based elderly subjects (aged 65 years) without dementia in New York provided dietary information and were prospectively evaluated with the same standardized neurological and neuropsychological measures approximately every 1.5 years. Using reduced rank regression, we calculated DPs based on their ability to explain variation in 7 potentially AD-related nutrients: saturated fatty acids, monounsaturated fatty acids, -3 polyunsaturated fatty acids, -6 polyunsaturated fatty acids, vitamin E, vitamin B12, and folate. The associations of reduced rank regression–derived DPs with AD risk were then examined using a Cox proportional hazards model.
Main Outcome Measure Incident AD risk.
Results Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years. We identified a DP strongly associated with lower AD risk: compared with subjects in the lowest tertile of adherence to this pattern, the AD hazard ratio (95% confidence interval) for subjects in the highest DP tertile was 0.62 (0.43-0.89) after multivariable adjustment (P for trend = .01). This DP was characterized by higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter.
Conclusion Simultaneous consideration of previous knowledge regarding potentially AD-related nutrients and multiple food groups can aid in identifying food combinations that are associated with AD risk.
SNIP...
In conclusion, we identified a DP that was strongly protective against the development of AD. The results of the current study indicate that higher consumption of certain foods (salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, dark and green leafy vegetables) and lower of others (high-fat dairy, red meat, organ meat, and butter) may be associated with a decreased risk of developing AD via a more favorable profile of nutrients (ie, lower ingestion of SFA and higher ingestion of PUFA, vitamin E, and folate). Our findings provide support for further exploration of food combination–based dietary behavior for the prevention of this important public health problem.
Published online: April 12, 2010 (doi:10.1001/archneurol.2010.84)
http://archneur.ama-assn.org/cgi/content/full/2010.84?home
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed", As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process, Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1.1
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
92/11.4/1.2
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of B amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Wednesday, March 31, 2010
Neurobiology of Disease Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases
http://betaamyloidcjd.blogspot.com/2010/03/neurobiology-of-disease-molecular-cross.html
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
P03.139
Cellular Prion Protein Regulates the ß-Secretase Cleavage of the Alzheimer’s Amyloid Precursor Protein
Hooper, NM1; Parkin, ET1; Watt, NT1; Baybutt, H2; Manson, J2; Hussain, I3; Turner, AJ1 1University of Leeds, Institute of Molecular and Cellular Biology, UK; 2Roslin Institute, Neuropathogenesis Unit, UK; 3GlaxoSmithKline, Neurodegeneration Research, UK
Background: The normal cellular function of the prion protein (PrP), the causative agent of the transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease (CJD) in humans, remains enigmatic. Several studies have reported combinations of Alzheimer’s Disease (AD) and CJD neuropathology and the Val/Met129 polymorphism in the PrP gene has been identified as a risk factor for early-onset AD, leading to speculation that there may be some pathogenic connection between these two neurodegenerative conditions. The amyloid ß (Aß) peptides that cause AD are derived from the amyloid precursor protein (APP) through sequential proteolytic cleavage by the ß-secretase (BACE1) and the g-secretase complex. Aim: As both APP and PrP are cleaved by zinc metalloproteases of the ADAM family, we investigated whether PrP alters the proteolytic processing of APP. Results: Here we show that expression of PrP in SH-SY5Y cells dramatically downregulated the cleavage of APP by BACE1 and reduced the secretion of Aß peptides into the conditioned medium by >92%. Conversely, siRNA reduction of endogenous PrP in N2a cells led to an increase in secreted Aß. Furthermore, levels of Aß were significantly increased in the brains of PrP null mice as compared with wild type mice. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases, did not inhibit the BACE1 cleavage of APP. To investigate whether the Val/Met129 polymorphism in human PrPC would alter the production of Aß, brains from mice with the human PrP gene with MM or VV 129 genotypes were analysed. In the MM mice there was a significant increase in Aß in the brains as compared with the VV mice. In the brains of two strains (79A and 87V) of scrapie-infected mice there was a significant increase in Aß peptides as compared to uninfected mice. Conclusions: Together these data reveal a novel function for PrP in regulating the processing of APP through inhibition of BACE1. The increase in APP processing in cells expressing disease-associated forms of PrP and in scrapie-infected brains raises the possibility that the increase in Aß may contribute to the neurodegeneration observed in prion diseases. Funded by the Medical Research Council of Great Britain.
P03.140
Prion Protein Regulates the ß-Secretase Cleavage of the Alzheimer’s Amyloid Precursor Protein through Interaction with Glycosaminoglycans
Griffiths, HH; Parkin, ET; Watt, NT; Turner, AJ; Hooper, NM University of Leeds, Institute of Molecular and Cellular Biology, UK
Background: Proteolytic processing of the amyloid precursor protein (APP) by ßsecretase, BACE1, is the initial step in the production of the amyloid ß (Aß) peptide which is involved in the pathogenesis of Alzheimer’s disease. We have shown that the cellular prion protein (PrP) inhibits the cleavage of APP by BACE1 in cell and animal models. Aim: To investigate the mechanism by which PrP inhibits the action of BACE1. Results: Neither PrPdeltaGPI, which is not membrane attached, nor PrP-CTM, which is anchored by a transmembrane domain and is excluded from cholesterol-rich lipid rafts, reduced cleavage of APP, suggesting that to inhibit the BACE1 cleavage of APP PrP has to be localised to lipid rafts. Coimmunoprecipitation experiments demonstrated that PrP physically interacts with BACE1. However, PrP did not alter the activity of BACE1 towards a fluorogenic peptide substrate nor perturb the dimerisation of BACE1. Using constructs of PrP lacking either the octapeptide repeats or the 4 residues KKRP at the N-terminus of the mature protein (PrPdeltaN), we demonstrate that the KKRP sequence but not the octapeptide repeats, is essential for regulating the BACE1 cleavage of APP. As the KKRP sequence is known to participate in glycosaminoglycan (GAG) binding, we confirmed that PrPdeltaN did not bind to immobilised heparin. Addition of heparin to SH-SY5Y cells increased the amount of APP cleaved by BACE1 in a concentration-dependent manner and reduced the amount of BACE1 coimmunoprecipitated with PrP, suggesting that GAGs are required for PrP to interact with BACE1 and inhibit APP processing. Of a range of GAGs, including dextran sulphate, hyaluronic acid and chondroitin sulphate, investigated there was complete correlation between those that could restore BACE1 cleavage of APP in PrP expressing cells and those that bound PrP. Conclusion: These data suggest a possible mechanism by which PrP regulates the ßcleavage of APP is through the N-terminus of PrP interacting via GAGs with one or more of the heparin binding sites on BACE1 within a subset of cholesterol-rich lipid rafts, thereby restricting access of BACE1 to APP. Funded by the Medical Research Council of Great Britain. P04.37 Comparison of the Neuropsychological Profile of Patients with Sporadic Creutzfeldt-Jakob Disease and Patients with Alzheimer’s Krzovska, M1; Cepek, L1; Ratzka, P2; Döhlinger, S3; Uttner, I1; Wolf, Stefanie4; Irle, Eva4; Mollenhauer, Brit5; Kretzschmar, Hans A.6; Riepe, Matthias7; v. Arnim, Christine1; Otto, Markus1 1University of Ulm, Germany; 2Department of Neurology, Germany; 3University of Goettingen, Germany; 4University of Goettingen, Germany; 5Elena Klinik, Germany; 6LMU, Germany; 7University of Berlin, Germany Background:To evaluate the neuropsychological profile of sCJD we administered the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) in order to determine if and how the sCJD-Subgroups (Met/Met, Met/Val, Val/Val) have different results in the item analysis of the ADAS-cog. Furthermore, we studied how the scores differ from that of patients with Alzheimer’s disease (AD). Methods:33 sCJD patients (11 with definite CJD and 22 with probable CJD) underwent neuropsychological testing with the ADAS-cog and Mini Mental State Exam (MMSE). Of these 31 were genotyped at the Codon 129 (11 Val/Val, 18 Met/Val and 2 Met/Met). The patients were matched in regards to sex and total ADAS-cog score with AD patients. The scores of the 11 ADAS-cog items were compared between the sCJD and the AD groups as well as between the sCJD-subgroups Met/Val and Val/Val and the AD group. Results:The ADAS-cog total score of the sCJD and AD groups was 22.6+/- 6.5, respectively. Regarding the single Item scores of the sCJD patient group and the AD patient group, there were statistically significant differences in the Items Constructional praxis, Word-finding difficulty in spontaneous speech and Spoken language ability. When comparing the sCJD subtypes with each other no statistically significant difference was found in the items. Conclusion: In the spee domain and constructional praxis there is indication of greater impairment in sCJD patients in general when compared with AD patients. A disturbance of the speech appears to be an important characteristic of the Met/Val and Val/Val subtypes of sCJD, and should therefore be the focus of special attention in future neuropsychological studies.
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
Article Posted: 04/15/2007 9:16:48 PM
Human and Animal Food Poisoning with Mad Cow a Slow Death
an editorial by Terry S. Singeltary Sr.
HUMAN AND ANIMAL FOOD POISONING WITH MAD COW DISEASEs A SLOW DEATH
WITH all the pet food deaths mounting from tainted pet food, all the suffering not only the animals are going through, but there owners as well, why are owners of these precious animals not crying about the mad cow tainted animal carcasses they poison there animals with everyday, and have been for decades, why not an uproar about that? well, let me tell you why, they don't drop dead immediately, it's a slow death, they simply call it FELINE and or CANINE ALZHEIMER'S DISEASE, DEMENTIA OR MAD CAT/DOG DISEASE i.e. FSE and they refuse to document CSE i.e.Canine Spongiform Encephalopathy, but it's there and there is some strange pathological findings on that topic that was convientantly swept under the rug. Sadly, this happens everyday with humans, once again confidently swept under the rug as Alzheimer's and or dementia i.e. fast Alzheimer's. Who wants to spend money on an autopsy on an old dog or cat? Sadly, it's the same with humans, you get old and demented your either die or your family puts you in an old folks home and forgets about you, then you die, and again, no autopsy in most cases. Imagine 4.5 annually with Alzheimer's, with and estimated 20+ million dieing a slow death by 2050, and in reality it will most likely be much higher than that now that the blood supply has been infiltrated with the TSE agent, and we now know that blood is another route and source for this hideous disease. It's hell getting old now a days.
NOW, for the ones that don't believe me, well mad cow has been in the USA for decades undetected officially, but the late Richard Marsh documented way back, again, swept under the rug. Then in 2003 in December, the first case of BSE was finally documented, by accident. Then you had the next two cases that were documented in Texas and Alabama, but it took an act of Congress, literally, to get those finally documented, and when they were finally documented, they were atypical BSE or Bovine Amyloid Spongiform Encephalopathy (BASE), which when transmitted to humans is not vCJD or nvCJD, but SPORADIC CJD. Now you might ask yourself what about that mad cow feed ban of August 4, 1997, the year my mother died from the Heidenhain Variant of Creutzfeldt Jakob Disease (confirmed), well that ruminant to ruminant was merely a regulation on paper that nobody enforced. Just last month there was 10+ PLUS MILLION POUNDS OF BANNED BLOOD TAINTED MBM DISPERSED INTO COMMERCE, and there is no way the FDA will ever recover it. It will be fed out again. 2006 was a banner year for FDA mad cow protein fed out into commerce. Looks like 2007 will be also. Our federal Government has failed us at every corner when it comes to food safety. maybe your dog, your cat, your mom, your dad, your aunt, or your uncle, but again, who cares, there old and demented, just put them down, or put them away. It's hell getting old. ...END
http://www.swnebr.net/newspaper/cgi-bin/articles/articlearchiver.pl?160273
Crushed heads (which inevitably involve brain and spinal cord material) are used to a limited extent but will also form one of the constituent raw materials of meat and bone meal, which is used extensively in pet food manufacturer...
http://collections.europarchive.org/tna/20080102163540/http://www.bseinquiry.gov.uk/files/yb/1989/03/17004001.pdf
http://www.swnebr.net/newspaper/cgi-bin/articles/articlearchiver.pl?160273
http://newhopetoday.blogspot.com/2007/04/article-posted-04152007-91648-pm-human.html
CANINE SPONGIFORM ENCEPHALOPATHY
http://caninespongiformencephalopathy.blogspot.com/
Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
Monday, January 4, 2010
Rising Tide: The Impact of Dementia in Canada Huge wave of dementia cases coming, warns report
http://betaamyloidcjd.blogspot.com/2010/01/rising-tide-impact-of-dementia-in.html
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
--------------------------------------------------------------------------------
Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
--------------------------------------------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
. Could cases of protease sensitive prionopathy (PSP) be mis
sed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?
. Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?
SNIP...
FULL TEXT ;
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
Sunday, June 7, 2009
ALZHEIMER'S DISEASE IS TRANSMISSIBLE
http://betaamyloidcjd.blogspot.com/2009/06/alzheimers-disease-is-transmissible.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Wednesday, April 14, 2010
Wednesday, March 31, 2010
Neurobiology of Disease Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases
Neurobiology of Disease Molecular Cross Talk between Misfolded Proteins in Animal Models of Alzheimer's and Prion Diseases
Rodrigo Morales,1,2,3 Lisbell D. Estrada,2,3 Rodrigo Diaz-Espinoza,1,2 Diego Morales-Scheihing,1 Maria C. Jara,1 Joaquin Castilla,2 and Claudio Soto1,2
1Protein Misfolding Disorders Laboratory, Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Medical School at Houston, Houston, Texas 77030, 2Protein Misfolding Disorders Laboratory, Department of Neurology, University of Texas Medical Branch, Galveston, Texas 77555, and 3Facultad de Ciencias, Universidad de Chile, Santiago, Chile
Correspondence should be addressed to Claudio Soto at the above address. Email: claudio.soto@uth.tmc.edu
The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein. Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration and exacerbation of both pathologies. The onset of prion disease symptoms in transgenic mice appeared significantly faster with a concomitant increase on the level of misfolded prion protein in the brain. A striking increase in amyloid plaque deposition was observed in prion-infected mice compared with their noninoculated counterparts. Histological and biochemical studies showed the association of the two misfolded proteins in the brain and in vitro experiments showed that protein misfolding can be enhanced by a cross-seeding mechanism. These results suggest a profound interaction between Alzheimer's and prion pathologies, indicating that one protein misfolding process may be an important risk factor for the development of a second one. Our findings may have important implications to understand the origin and progression of PMDs.
-------------------------------------------------------------------------------- Received Nov. 30, 2009; revised Jan. 22, 2010; accepted Feb. 2, 2010.
Correspondence should be addressed to Claudio Soto at the above address. Email: claudio.soto@uth.tmc.edu
http://www.jneurosci.org/cgi/content/abstract/30/13/4528?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=30&issue=13&resourcetype=HWCIT
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed", As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process, Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1.1
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
92/11.4/1.2
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of B amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Friday, March 5, 2010
Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring
http://betaamyloidcjd.blogspot.com/2010/03/fatal-transmissible-amyloid.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
TSS
Rodrigo Morales,1,2,3 Lisbell D. Estrada,2,3 Rodrigo Diaz-Espinoza,1,2 Diego Morales-Scheihing,1 Maria C. Jara,1 Joaquin Castilla,2 and Claudio Soto1,2
1Protein Misfolding Disorders Laboratory, Department of Neurology, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, University of Texas Medical School at Houston, Houston, Texas 77030, 2Protein Misfolding Disorders Laboratory, Department of Neurology, University of Texas Medical Branch, Galveston, Texas 77555, and 3Facultad de Ciencias, Universidad de Chile, Santiago, Chile
Correspondence should be addressed to Claudio Soto at the above address. Email: claudio.soto@uth.tmc.edu
The central event in protein misfolding disorders (PMDs) is the accumulation of a misfolded form of a naturally expressed protein. Despite the diversity of clinical symptoms associated with different PMDs, many similarities in their mechanism suggest that distinct pathologies may cross talk at the molecular level. The main goal of this study was to analyze the interaction of the protein misfolding processes implicated in Alzheimer's and prion diseases. For this purpose, we inoculated prions in an Alzheimer's transgenic mouse model that develop typical amyloid plaques and followed the progression of pathological changes over time. Our findings show a dramatic acceleration and exacerbation of both pathologies. The onset of prion disease symptoms in transgenic mice appeared significantly faster with a concomitant increase on the level of misfolded prion protein in the brain. A striking increase in amyloid plaque deposition was observed in prion-infected mice compared with their noninoculated counterparts. Histological and biochemical studies showed the association of the two misfolded proteins in the brain and in vitro experiments showed that protein misfolding can be enhanced by a cross-seeding mechanism. These results suggest a profound interaction between Alzheimer's and prion pathologies, indicating that one protein misfolding process may be an important risk factor for the development of a second one. Our findings may have important implications to understand the origin and progression of PMDs.
-------------------------------------------------------------------------------- Received Nov. 30, 2009; revised Jan. 22, 2010; accepted Feb. 2, 2010.
Correspondence should be addressed to Claudio Soto at the above address. Email: claudio.soto@uth.tmc.edu
http://www.jneurosci.org/cgi/content/abstract/30/13/4528?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=30&issue=13&resourcetype=HWCIT
BSE101/1 0136
IN CONFIDENCE
CMO
From: Dr J S Metters DCMO
4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognised the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed", As the report emphasises the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process, Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1.1
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
J S METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
92/11.4/1.2
http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight
Date: 5 January 1993
Copies:
Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of B amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Friday, March 5, 2010
Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring
http://betaamyloidcjd.blogspot.com/2010/03/fatal-transmissible-amyloid.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
TSS
Friday, March 5, 2010
Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring
Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring
Bruce Chesebro1*, Brent Race1, Kimberly Meade-White1, Rachel LaCasse1, Richard Race1, Mikael Klingeborn1, James Striebel1, David Dorward2, Gillian McGovern3, Martin Jeffrey3
1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America, 2 Electron Microscopy Section, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America, 3 VLA (Lasswade), Penicuik, Scotland, United Kingdom
Abstract
Prion diseases are fatal neurodegenerative diseases of humans and animals characterized by gray matter spongiosis and accumulation of aggregated, misfolded, protease-resistant prion protein (PrPres). PrPres can be deposited in brain in an amyloid-form and/or non-amyloid form, and is derived from host-encoded protease-sensitive PrP (PrPsen), a protein normally anchored to the plasma membrane by glycosylphosphatidylinositol (GPI). Previously, using heterozygous transgenic mice expressing only anchorless PrP, we found that PrP anchoring to the cell membrane was required for typical clinical scrapie. However, in the present experiments, using homozygous transgenic mice expressing two-fold more anchorless PrP, scrapie infection induced a new fatal disease with unique clinical signs and altered neuropathology, compared to non-transgenic mice expressing only anchored PrP. Brain tissue of transgenic mice had high amounts of infectivity, and histopathology showed dense amyloid PrPres plaque deposits without gray matter spongiosis. In contrast, infected non-transgenic mice had diffuse non-amyloid PrPres deposits with significant gray matter spongiosis. Brain graft studies suggested that anchored PrPsen expression was required for gray matter spongiosis during prion infection. Furthermore, electron and light microscopic studies in infected transgenic mice demonstrated several pathogenic processes not seen in typical prion disease, including cerebral amyloid angiopathy and ultrastructural alterations in perivascular neuropil. These findings were similar to certain human familial prion diseases as well as to non-prion human neurodegenerative diseases, such as Alzheimer's disease.
Author Summary
Prion diseases, also known as transmissible spongiform encephalopathies, are infectious fatal neurodegenerative diseases of humans and animals. A major feature of prion diseases is the refolding and aggregation of a normal host protein, prion protein (PrP), into a disease-associated form which may contribute to brain damage. In uninfected individuals, normal PrP is anchored to the outer cell membrane by a sugar-phosphate-lipid linker molecule. In the present report we show that prion infection of mice expressing PrP lacking the anchor can result in a new type of fatal neurodegenerative disease. This disease displays mechanisms of damage to brain cells and brain blood vessels found in Alzheimer's disease and in familial amyloid brain diseases. In contrast, the typical sponge-like brain damage seen in prion diseases was not observed. These results suggest that presence or absence of PrP membrane anchoring can influence the type of neurodegeneration seen after prion infection.
Citation: Chesebro B, Race B, Meade-White K, LaCasse R, Race R, et al. (2010) Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring. PLoS Pathog 6(3): e1000800. doi:10.1371/journal.ppat.1000800
Editor: David Westaway, University of Alberta, Canada
Received: September 25, 2009; Accepted: January 29, 2010; Published: March 5, 2010
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: Funded by the Intramural program of NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: bchesebro@nih.gov
see full text here;
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000800
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
TSS
Bruce Chesebro1*, Brent Race1, Kimberly Meade-White1, Rachel LaCasse1, Richard Race1, Mikael Klingeborn1, James Striebel1, David Dorward2, Gillian McGovern3, Martin Jeffrey3
1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America, 2 Electron Microscopy Section, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America, 3 VLA (Lasswade), Penicuik, Scotland, United Kingdom
Abstract
Prion diseases are fatal neurodegenerative diseases of humans and animals characterized by gray matter spongiosis and accumulation of aggregated, misfolded, protease-resistant prion protein (PrPres). PrPres can be deposited in brain in an amyloid-form and/or non-amyloid form, and is derived from host-encoded protease-sensitive PrP (PrPsen), a protein normally anchored to the plasma membrane by glycosylphosphatidylinositol (GPI). Previously, using heterozygous transgenic mice expressing only anchorless PrP, we found that PrP anchoring to the cell membrane was required for typical clinical scrapie. However, in the present experiments, using homozygous transgenic mice expressing two-fold more anchorless PrP, scrapie infection induced a new fatal disease with unique clinical signs and altered neuropathology, compared to non-transgenic mice expressing only anchored PrP. Brain tissue of transgenic mice had high amounts of infectivity, and histopathology showed dense amyloid PrPres plaque deposits without gray matter spongiosis. In contrast, infected non-transgenic mice had diffuse non-amyloid PrPres deposits with significant gray matter spongiosis. Brain graft studies suggested that anchored PrPsen expression was required for gray matter spongiosis during prion infection. Furthermore, electron and light microscopic studies in infected transgenic mice demonstrated several pathogenic processes not seen in typical prion disease, including cerebral amyloid angiopathy and ultrastructural alterations in perivascular neuropil. These findings were similar to certain human familial prion diseases as well as to non-prion human neurodegenerative diseases, such as Alzheimer's disease.
Author Summary
Prion diseases, also known as transmissible spongiform encephalopathies, are infectious fatal neurodegenerative diseases of humans and animals. A major feature of prion diseases is the refolding and aggregation of a normal host protein, prion protein (PrP), into a disease-associated form which may contribute to brain damage. In uninfected individuals, normal PrP is anchored to the outer cell membrane by a sugar-phosphate-lipid linker molecule. In the present report we show that prion infection of mice expressing PrP lacking the anchor can result in a new type of fatal neurodegenerative disease. This disease displays mechanisms of damage to brain cells and brain blood vessels found in Alzheimer's disease and in familial amyloid brain diseases. In contrast, the typical sponge-like brain damage seen in prion diseases was not observed. These results suggest that presence or absence of PrP membrane anchoring can influence the type of neurodegeneration seen after prion infection.
Citation: Chesebro B, Race B, Meade-White K, LaCasse R, Race R, et al. (2010) Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring. PLoS Pathog 6(3): e1000800. doi:10.1371/journal.ppat.1000800
Editor: David Westaway, University of Alberta, Canada
Received: September 25, 2009; Accepted: January 29, 2010; Published: March 5, 2010
This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
Funding: Funded by the Intramural program of NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: bchesebro@nih.gov
see full text here;
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000800
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
TSS
Monday, January 4, 2010
Rising Tide: The Impact of Dementia in Canada
Huge wave of dementia cases coming, warns report
CTV.ca News Staff
Date: Mon. Jan. 4 2010 9:52 AM ET
So many Canadians are expected to develop Alzheimer's disease and dementia in the next 30 years that a new case will be diagnosed every two minutes unless preventive measures are taken, a new report says.
The report, released Monday by the Alzheimer Society, says the prevalence of dementia will more than double in the next 30 years.
By 2038, almost three per cent of Canada's population will be affected by dementia, and about 257,800 new cases will be diagnosed per year.
Today, dementia costs Canada about $15 billion a year; those costs could soon increase by 10-fold.
"If nothing changes, this sharp increase in the number of people living with dementia will mean that by 2038, the total costs associated with dementia will reach $153 billion a year," David Harvey, principal spokesperson for the Alzheimer Society project called "Rising Tide: The Impact of Dementia on Canadian Society," said in a statement.
That amounts to a cumulative total of $872 billion over the 30-year period.
Much of the increase in cases can be attributed to the "greying" of Canada. With Canadians living longer and baby boomers aging, there is expected to be a spike in many chronic diseases that come with age, such as heart disease, arthritis and cancer.
But the expected rising rates of dementia are not just about demographics; poor lifestyles also play a role.
It's been well documented that regular physical and mental exercise can delay the onset of dementia, which includes Alzheimer's disease and other progressive diseases that destroy brain cells. For that reason, the report recommends that all Canadians over 65 without dementia increase their physical activity by 50 per cent.
"Prevention is where we need to be starting," Harvey told Canada AM.
"We know that healthy eating and active living are antidotes to dementia."
The "Rising Tide" report calls on government to fund more health promotion to remind Canadians of the benefits of a healthy lifestyle.
"This intervention would reduce the number of people diagnosed with dementia, resulting in a reduction in the pressure on long-term care facilities, community care services and informal caregivers," the report says.
Need for national strategy
Just as important, Harvey says, is the need for Canada's health care system to adapt to accommodate the projected rise in dementia cases.
"Dementia is one of the leading cases of disability amongst older people," Harvey said, noting that the flood of dementia expected in the next 30 years could overwhelm emergency rooms and hospitals.
His group's report calls for more support for informal caregivers -- generally, family members -- who tend to be the ones who care for patients with dementia in the early stages of the disease.
"There are services that can be put in place to support caregivers, and also economic and financial support for caregivers," he said.
By also providing caregivers with skill-building and support programs, caregivers struggling with the overwhelming emotional and financial hardships of providing care may feel better equipped to care for their loved one.
That could go far to delay admission of patients into long-term care facilities, thereby lessening the burden on the health care system.
The report also suggests assigning "system navigators" to each newly diagnosed dementia patient and their caregivers. These case managers would help families navigate the health system to find the right social services for their loved one depending on their stage of dementia.
--------------------------------------------------------------------------------
Some facts about dementia:
The symptoms of dementia include a gradual and continuing decline of memory, changes in judgment or reasoning, mood and behaviour, and an inability to perform familiar tasks. Dementia can strike adults at any age, but has traditionally been diagnosed in people over 65. However, symptoms start much earlier, and an increasing number of people are being diagnosed in their 50s and early 60s. Age is the number one risk factor for dementia Alzheimer's disease, the most common form of dementia, accounts for approximately 64 per cent of all dementias in Canada. Other related dementias include Vascular Dementia, Frontotemporal Dementia, Creutzfeldt-Jakob Disease and Lewy body Dementia. There is no known cure for dementia. However, some medications can delay progression of the disease. Researchers are confident that within five to seven years, there will be treatments that attack the disease process itself, not just the symptoms.
http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20100104/dementia_surge_100104/20100104?hub=Health
Report Summary Rising Tide: The Impact of Dementia in Canada In this section :
Read a summary of Rising Tide: The Impact of Dementia in Canada
Download Rising Tide: The Impact of Dementia in Canada Rising Tide: the Impact of Dementia on Canadian Society is the final report of an Alzheimer Society project funded by Pfizer Canada, Health Canada, Public Health Agency of Canada, Canadian Institutes of Health Research and Rx&D. The purpose of the report was to:
Estimate the health and economic burden of dementia in Canada over the next 30 years; Analyze the possible effects of intervention scenarios upon this burden; Demonstrate how the proposed interventions could affect the health and economic impacts of dementia in Canada; Review policy options; Make recommendations on how to address the issue. The Findings of Rising Tide1 Health Burden of Dementia for Canada: 2008-2038²
Incidence of Alzheimer's disease and related dementias in Canada: 2008 - 103,700 new cases per year (1 every 5 minutes) 2038 - 257,800 new cases per year (1 every 2 minutes) Prevalence of Alzheimer's disease and related dementias in Canada: 2008 - 480,600 people with dementia (1.5% of Canada's population) 2038 - 1,125,200 people with dementia (2.8% of Canada's population) View the prevalence of dementia by age graph
View the prevalence of dementia by sex graph
Hours of informal care provided annually for people with dementia in Canada 2008 - 231 million hours 2038 - 756 million hours Economic Consequences of Dementia for Canada: 2008-2038²
The Economic Burden of dementia doubles every decade, increasing from $15 billion in 2008 to a startling $153 billion in 2038.
Economic Burden of Dementia (in future dollars) 2008 - $15 billion 2018 - $37 billion 2028 - $75 billion 2038 - $153 billion
Cumulative Consequences of Dementia over a 30-year period
Cumulative data represents the combined total of either the economic costs of dementia per year, or the number of people developing dementia per year, each year between 2008 and 2038. By 2038, the cumulative incidence of dementia will be more than 5.5 million people³, with a cumulative economic cost of $872 billion² (2008 dollars).
Implications – What can Canada do? What Has Been Done Elsewhere
Across the globe, many countries are recognizing the urgent issue of dementia. Australia, Norway, the Netherlands, France, Scotland and the United Kingdom have recently developed specific plans or frameworks for dealing with dementia.
View Alzheimer Disease International's graphs correlating research effort with contributions to mortality and disability.
Intervention Opportunities
Recognizing the urgent need to start turning the tide of dementia, Rising Tide describes four potential intervention scenarios, backed by current evidence that could become critical factors in reducing the impact of dementia.
The report tested the impact of four potential intervention scenarios:
Increasing Physical Activity Delay Onset of Dementia Caregiver Training, Support System Navigation All showed the potential for dramatic reductions in economic impact over the next 30 years.
Note: Rising Tide was undertaken in order to alert the Canadian public and federal, provincial and territorial politicians of the need for policies and approaches to address the looming dementia crisis. In the reports, you will find four suggested interventions. They are not meant to be definitive but to serve as illustrations of how the base case can be used to inform and shape policy in this field. The 5 recommendations in the report were developed through a comprehensive process of consultations with subject experts and stakeholders. The underlying message is that we must act now and that change is possible.
Recommendations
Rising Tide also makes five recommendations that would make up the components of a comprehensive National Dementia Strategy. They include:
An accelerated investment in all areas of dementia research. A clear recognition of the important role played by informal caregivers. An increased recognition of the importance of prevention and early intervention. Greater integration of care and increased use of chronic disease prevention and management. A strengthening of Canada's dementia workforce.
Download a copy of Rising Tide: The Impact of Dementia on Canadian Society.
Endnotes
Rising Tide: Impact of Dementia on Canadian Society is a report based on a study conducted by RiskAnalytica, a leading firm in risk management. RiskAnalytica's Life at Risk® simulation platform was customized for the Rising Tide study based on the latest dementia and health economic research, validated for epidemiological and economic aspects by subject matter experts and checked for data, logic and results. The simulation platform was then run to establish the Base Case, or the findings. Rising Tide: The Impact of Dementia on Canadian Society. Alzheimer Society, 2009. Smetanin, P., Kobak, P., Briante, C., Stiff, D., Sherman, G., and Ahmad, S. Rising Tide: The Impact of Dementia in Canada 2008 to 2038. RiskAnalytica, 2009.
http://www.alzheimer.ca/english/rising_tide/rising_tide_summary.htm
http://www.alzheimer.ca/english/rising_tide/rising_tide_report.htm
SEE FULL REPORT HERE ;
Rising Tide:
The Impact of Dementia on Canadian Society
Executive Summary
http://www.alzheimer.ca/docs/RisingTide/AS%20Rising%20Tide-Executive%20Summary_Eng_FINAL_SecuredVersion.pdf
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
SEAC OCTOBER 2009
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
http://www.seac.gov.uk/pdf/hol-response091008.pdf
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...
snip...
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf
And NONE of this is relevant to BSE?
There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://web.archive.org/web/20010305223143/www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
also, see the increase of Alzheimer's from 1981 to 1986
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
see full text ;
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients Copyright © 2009 Published by Elsevier Inc.
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
----- Original Message -----
From: "Terry S. Singeltary Sr." To: Sent: Monday, October 12, 2009 9:47 AM Subject: [BSE-L] SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
snip...
. More specific examples of unanswered questions with health implications are:
. Will the eventual elimination of classical scrapie in the EU leave an ecological niche for other TSEs such as BSE or atypical scrapie?
. Is CWD transmissible to humans?
. Can a reliable ante mortem diagnostic blood test for vCJD be developed?
. What is the true prevalence of v CJD infection (as opposed to overt disease) in the UK?
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
--------------------------------------------------------------------------------
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
--------------------------------------------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
. Could cases of protease sensitive prionopathy (PSP) be missed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?
. Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?
SNIP...
FULL TEXT ;
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Monday, June 29, 2009 2:08 PM
Subject: [BSE-L] Beyond the prion principle
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
News and Views Nature 459, 924-925 (18 June 2009) doi:10.1038/459924a; Published online 17 June 2009
CELL BIOLOGY
Beyond the prion principle
Adriano Aguzzi
It seems that many misfolded proteins can act like prions - spreading disease by imparting their misshapen structure to normal cellular counterparts. But how common are bona fide prions really?
The protein-only hypothesis of prion propagation is steadily gaining ground. First envisaged by John Stanley Griffith1 and later formalized by Stanley Prusiner2, this theory proposes the existence of an infectious agent composed solely of protein. Three reports, two in Nature Cell Biology3,4 and one in The Journal of Cell Biology5, now contend that, far from being confined to the rare prion diseases, prion-like transmission of altered proteins may occur in several human diseases of the brain and other organs.
Prions are now accepted as causing the transmissible spongiform encephalopathies, which include scrapie in sheep, bovine spongiform encephalopathy (BSE, or mad cow disease) and its human variant Creutzfeldt-Jakob disease. The infectious prion particle is made up of PrPSc, a misfolded and aggregated version of a normal protein known as PrPC. Like the growth of crystals, PrPSc propagates by recruiting monomeric PrPC into its aggregates - a process that has been replicated in vitro6 and in transgenic mice7. The breakage of PrPSc aggregates represents the actual replicative event, as it multiplies the number of active seeds8.
Apart from prion diseases, the misfolding and aggregation of proteins into various harmful forms, which are collectively known as amyloid, causes a range of diseases of the nervous system and other organs. The clinical characteristics of amyloidoses, however, gave little reason to suspect a relationship to prion diseases. Hints of prion-like behaviour in amyloid have emerged from studies of Alzheimer's disease and Parkinson's disease. Alzheimer's disease had been suspected to be transmissible for some time: an early report9 of disease transmission to hamsters through white blood cells from people with Alzheimer's disease caused great consternation, but was never reproduced. Much more tantalizing evidence came from the discovery10,11 that aggregates of the amyloid-â (Aâ) peptide found in the brain of people with Alzheimer's disease could be transmitted to the brain of mice engineered to produce large amounts of the Aâ precursor protein APP. Another study12 has shown that healthy tissue grafted into the brain of people with Parkinson's disease acquires intracellular Lewy bodies - aggregates of the Parkinson's disease-associated protein á-synuclein. This suggests prion-like transmission of diseased protein from the recipient's brain to the grafted cells.
These findings10-12 raise a provocative question. If protein aggregation depends on the introduction of 'seeds' and on the availability of the monomeric precursor, and if, as has been suggested13, amyloid represents the primordial state of all proteins, wouldn't all proteins - under appropriate conditions - behave like prions in the presence of sufficient precursor? Acceptance of this concept is gaining momentum. For one thing, an increasing wealth of traits is being found in yeast, fungi and bacteria that can best be explained as prion-like phenomena (see table). And now, Ren and colleagues3 provide evidence for prion-like spread of polyglutamine (polyQ)- containing protein aggregates, which are similar to the aggregates found in Huntington's disease. They show that polyQ aggregates can be taken up from the outside by mammalian cells. Once in the cytosol, the polyQ aggregates can grow by recruiting endogenous polyQ. Clavaguera et al.4 report similar findings in a mouse model of tauopathy, a neurodegenerative disease caused by intraneuronal aggregation of the microtubule-associated tau protein. Injection of mutant human tau into the brain of mice overexpressing normal human tau transmitted tauopathy, with intracellular aggregation of previously normal tau and spread of aggregates to neighbouring regions of the brain. Notably, full-blown tauopathy was not induced in mice that did not express human tau. Assuming that tau pathology wasn't elicited by some indirect pathway (some mice overexpressing mutated human tau develop protein tangles even when exposed to un related amyloid aggregates14), this sequence of events is reminiscent of prions. Finally, Frost and colleagues5 show that extracellular tau aggregates can be taken up by cells in culture. Hence, tau can attack and penetrate cells from the outside, sporting predatory behaviour akin to that of prions.
Yet there is one crucial difference between actual prion diseases and diseases caused by other prion-like proteins (let's call them prionoids) described so far (see table). The behaviour of prions is entirely comparable to that of any other infectious agent: for instance, prions are transmissible between individuals and often across species, and can be assayed with classic microbiological techniques, including titration by bioassay. Accordingly, prion diseases were long thought to be caused by viruses, and BSE created a worldwide panic similar to that currently being provoked by influenza. By contrast, although prionoids can 'infect' neighbouring molecules and sometimes even neighbouring cells, they do not spread within communities or cause epidemics such as those seen with BSE.
So, should any amyloid deserve an upgrade to a bone fide prion status? Currently, amyloid A (AA) amyloidosis may be the most promising candidate for a truly infectious disease caused by a self-propagating protein other than PrPSc. AA amyloid consists of orderly aggregated fragments of the SAA protein, and its deposition damages many organs of the body. Seeds of AA amyloid can be excreted in faeces15, and can induce amyloidosis if taken up orally (at least in geese)16. Also, AA amyloid may be transmitted between mice by transfusion of white blood cells17. So, like entero viruses and, perhaps, sheep scrapie prions, AA amyloid seems to display all the elements of a complete infectious life cycle, including uptake, replication and release from its host.
There are intriguing evolutionary implications to the above findings. If prionoids are ubiquitous, why didn't evolution erect barriers to their pervasiveness? Maybe it is because the molecular transmissibility of aggregated states can sometimes be useful. Indeed, aggregation of the Sup35 protein, which leads to a prion-like phenomenon in yeast, may promote evolutionary adaptation by allowing yeast cells to temporarily activate DNA sequences that are normally untranslated18. Mammals have developed receptors for aggregates, and ironically PrPC may be one of them19, although these receptors have not been reported to mediate protective functions. Therefore, we shouldn't be shocked if instances of beneficial prionoids emerge in mammals as well. ¦
Adriano Aguzzi is at the Institute of Neuropathology, University Hospital of Zurich, CH-8091 Zurich, Switzerland. e-mail: adriano.aguzzi@usz.ch
1. Griffith, J. S. Nature 215, 1043-1044 (1967). 2. Prusiner, S. B. Science 216, 136-144 (1982). 3. Ren, P.-H. et al. Nature Cell Biol. 11, 219-225 (2009). 4. Clavaguera, F. et al. Nature Cell Biol. doi:10.1038/ncb1901 (2009). 5. Frost, B., Jacks, R. L. & Diamond, M. I. J. Biol. Chem. 284, 12845-12852 (2009). 6. Castilla, J., Saá, P., Hetz, C. & Soto, C. Cell 121, 195-206 (2005). 7. Sigurdson, C. J. et al. Proc. Natl Acad. Sci. USA 106, 304-309 (2009). 8. Aguzzi, A. & Polymenidou, M. Cell 116, 313-327 (2004). 9. Manuelidis, E. E. et al. Proc. Natl Acad. Sci. USA 85, 4898-4901 (1988). 10. Kane, M. D. et al. J. Neurosci. 20, 3606-3611 (2000). 11. Meyer-Luehmann, M. et al. Science 313, 1781-1784 (2006). 12. Li, J.-Y. et al. Nature Med. 14, 501-503 (2008). 13. Chiti, F. & Dobson, C. M. Annu. Rev. Biochem. 75, 333-366 (2006). 14. GÖtz, J., Chen, F., van Dorpe, J. & Nitsch, R. M. Science 293, 1491-1495 (2001). 15. Zhang, B. et al. Proc. Natl Acad. Sci. USA 105, 7263-7268 (2008). 16. Solomon, A. et al. Proc. Natl Acad. Sci. USA 104, 10998-11001 (2007). 17. Sponarova, J., NystrÖm, S. N. & Westermark, G. T. PLoS ONE 3, e3308 (2008). 18. True, H. L. & Lindquist, S. L. Nature 407, 477-483 (2000). 19. Laurén, J. et al. Nature 457, 1128-1132 (2009).
PRIONS AND POTENTIAL PRIONOIDS
Disease Protein Molecular transmissibility Infectious life cycle Prion diseases PrPSc Yes Yes Alzheimer's disease Amyloid-ß Yes Not shown Tauopathies Tau Yes Not shown Parkinson's disease a-Synuclein Host-to-graft Not shown AA amyloidosis Amyloid A Yes Possible Huntington's disease Polyglutamine Yes Not shown Phenotype Protein Molecular transmissibility Infectious life cycle Suppressed translational termination (yeast) Sup35 Yes Not shown Heterokaryon incompatibility (filamentous fungi) Het-s Yes Not shown Biofilm promotion (bacteria) CsgA Yes Not shown In humans and animals, infectious prion diseases are caused by PrPSc, which spreads by recruiting its monomeric precursor PrPC into aggregates. Aggregates then multiply by breakage, a process that is termed molecular transmissibility. Other proteins involved in disease and in phenotypes of fungi and bacteria, can also undergo self-sustaining aggregation, but none of these 'prionoid' proteins behaves like typical infectious agents, nor do any of them enact a complete infectious life cycle - with the possible exception of AA amyloid. Correction In the News & Views article "Immunology: Immunity's ancient arms" by Gary W. Litman and John P. Cannon (Nature 459, 784-786; 2009), the name of the fi rst author of the Nature paper under discussion was misspelt. The author's name is P. Guo, not Gou as published.
© 2009 Macmillan Publishers Limited. All rights reserved
http://www.nature.com/nature/journal/v459/n7249/full/459924a.html
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
Friday, January 01, 2010
Human Prion Diseases in the United States PART 1
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
my comments to PLosone here ;
http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd
TSS
CTV.ca News Staff
Date: Mon. Jan. 4 2010 9:52 AM ET
So many Canadians are expected to develop Alzheimer's disease and dementia in the next 30 years that a new case will be diagnosed every two minutes unless preventive measures are taken, a new report says.
The report, released Monday by the Alzheimer Society, says the prevalence of dementia will more than double in the next 30 years.
By 2038, almost three per cent of Canada's population will be affected by dementia, and about 257,800 new cases will be diagnosed per year.
Today, dementia costs Canada about $15 billion a year; those costs could soon increase by 10-fold.
"If nothing changes, this sharp increase in the number of people living with dementia will mean that by 2038, the total costs associated with dementia will reach $153 billion a year," David Harvey, principal spokesperson for the Alzheimer Society project called "Rising Tide: The Impact of Dementia on Canadian Society," said in a statement.
That amounts to a cumulative total of $872 billion over the 30-year period.
Much of the increase in cases can be attributed to the "greying" of Canada. With Canadians living longer and baby boomers aging, there is expected to be a spike in many chronic diseases that come with age, such as heart disease, arthritis and cancer.
But the expected rising rates of dementia are not just about demographics; poor lifestyles also play a role.
It's been well documented that regular physical and mental exercise can delay the onset of dementia, which includes Alzheimer's disease and other progressive diseases that destroy brain cells. For that reason, the report recommends that all Canadians over 65 without dementia increase their physical activity by 50 per cent.
"Prevention is where we need to be starting," Harvey told Canada AM.
"We know that healthy eating and active living are antidotes to dementia."
The "Rising Tide" report calls on government to fund more health promotion to remind Canadians of the benefits of a healthy lifestyle.
"This intervention would reduce the number of people diagnosed with dementia, resulting in a reduction in the pressure on long-term care facilities, community care services and informal caregivers," the report says.
Need for national strategy
Just as important, Harvey says, is the need for Canada's health care system to adapt to accommodate the projected rise in dementia cases.
"Dementia is one of the leading cases of disability amongst older people," Harvey said, noting that the flood of dementia expected in the next 30 years could overwhelm emergency rooms and hospitals.
His group's report calls for more support for informal caregivers -- generally, family members -- who tend to be the ones who care for patients with dementia in the early stages of the disease.
"There are services that can be put in place to support caregivers, and also economic and financial support for caregivers," he said.
By also providing caregivers with skill-building and support programs, caregivers struggling with the overwhelming emotional and financial hardships of providing care may feel better equipped to care for their loved one.
That could go far to delay admission of patients into long-term care facilities, thereby lessening the burden on the health care system.
The report also suggests assigning "system navigators" to each newly diagnosed dementia patient and their caregivers. These case managers would help families navigate the health system to find the right social services for their loved one depending on their stage of dementia.
--------------------------------------------------------------------------------
Some facts about dementia:
The symptoms of dementia include a gradual and continuing decline of memory, changes in judgment or reasoning, mood and behaviour, and an inability to perform familiar tasks. Dementia can strike adults at any age, but has traditionally been diagnosed in people over 65. However, symptoms start much earlier, and an increasing number of people are being diagnosed in their 50s and early 60s. Age is the number one risk factor for dementia Alzheimer's disease, the most common form of dementia, accounts for approximately 64 per cent of all dementias in Canada. Other related dementias include Vascular Dementia, Frontotemporal Dementia, Creutzfeldt-Jakob Disease and Lewy body Dementia. There is no known cure for dementia. However, some medications can delay progression of the disease. Researchers are confident that within five to seven years, there will be treatments that attack the disease process itself, not just the symptoms.
http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20100104/dementia_surge_100104/20100104?hub=Health
Report Summary Rising Tide: The Impact of Dementia in Canada In this section :
Read a summary of Rising Tide: The Impact of Dementia in Canada
Download Rising Tide: The Impact of Dementia in Canada Rising Tide: the Impact of Dementia on Canadian Society is the final report of an Alzheimer Society project funded by Pfizer Canada, Health Canada, Public Health Agency of Canada, Canadian Institutes of Health Research and Rx&D. The purpose of the report was to:
Estimate the health and economic burden of dementia in Canada over the next 30 years; Analyze the possible effects of intervention scenarios upon this burden; Demonstrate how the proposed interventions could affect the health and economic impacts of dementia in Canada; Review policy options; Make recommendations on how to address the issue. The Findings of Rising Tide1 Health Burden of Dementia for Canada: 2008-2038²
Incidence of Alzheimer's disease and related dementias in Canada: 2008 - 103,700 new cases per year (1 every 5 minutes) 2038 - 257,800 new cases per year (1 every 2 minutes) Prevalence of Alzheimer's disease and related dementias in Canada: 2008 - 480,600 people with dementia (1.5% of Canada's population) 2038 - 1,125,200 people with dementia (2.8% of Canada's population) View the prevalence of dementia by age graph
View the prevalence of dementia by sex graph
Hours of informal care provided annually for people with dementia in Canada 2008 - 231 million hours 2038 - 756 million hours Economic Consequences of Dementia for Canada: 2008-2038²
The Economic Burden of dementia doubles every decade, increasing from $15 billion in 2008 to a startling $153 billion in 2038.
Economic Burden of Dementia (in future dollars) 2008 - $15 billion 2018 - $37 billion 2028 - $75 billion 2038 - $153 billion
Cumulative Consequences of Dementia over a 30-year period
Cumulative data represents the combined total of either the economic costs of dementia per year, or the number of people developing dementia per year, each year between 2008 and 2038. By 2038, the cumulative incidence of dementia will be more than 5.5 million people³, with a cumulative economic cost of $872 billion² (2008 dollars).
Implications – What can Canada do? What Has Been Done Elsewhere
Across the globe, many countries are recognizing the urgent issue of dementia. Australia, Norway, the Netherlands, France, Scotland and the United Kingdom have recently developed specific plans or frameworks for dealing with dementia.
View Alzheimer Disease International's graphs correlating research effort with contributions to mortality and disability.
Intervention Opportunities
Recognizing the urgent need to start turning the tide of dementia, Rising Tide describes four potential intervention scenarios, backed by current evidence that could become critical factors in reducing the impact of dementia.
The report tested the impact of four potential intervention scenarios:
Increasing Physical Activity Delay Onset of Dementia Caregiver Training, Support System Navigation All showed the potential for dramatic reductions in economic impact over the next 30 years.
Note: Rising Tide was undertaken in order to alert the Canadian public and federal, provincial and territorial politicians of the need for policies and approaches to address the looming dementia crisis. In the reports, you will find four suggested interventions. They are not meant to be definitive but to serve as illustrations of how the base case can be used to inform and shape policy in this field. The 5 recommendations in the report were developed through a comprehensive process of consultations with subject experts and stakeholders. The underlying message is that we must act now and that change is possible.
Recommendations
Rising Tide also makes five recommendations that would make up the components of a comprehensive National Dementia Strategy. They include:
An accelerated investment in all areas of dementia research. A clear recognition of the important role played by informal caregivers. An increased recognition of the importance of prevention and early intervention. Greater integration of care and increased use of chronic disease prevention and management. A strengthening of Canada's dementia workforce.
Download a copy of Rising Tide: The Impact of Dementia on Canadian Society.
Endnotes
Rising Tide: Impact of Dementia on Canadian Society is a report based on a study conducted by RiskAnalytica, a leading firm in risk management. RiskAnalytica's Life at Risk® simulation platform was customized for the Rising Tide study based on the latest dementia and health economic research, validated for epidemiological and economic aspects by subject matter experts and checked for data, logic and results. The simulation platform was then run to establish the Base Case, or the findings. Rising Tide: The Impact of Dementia on Canadian Society. Alzheimer Society, 2009. Smetanin, P., Kobak, P., Briante, C., Stiff, D., Sherman, G., and Ahmad, S. Rising Tide: The Impact of Dementia in Canada 2008 to 2038. RiskAnalytica, 2009.
http://www.alzheimer.ca/english/rising_tide/rising_tide_summary.htm
http://www.alzheimer.ca/english/rising_tide/rising_tide_report.htm
SEE FULL REPORT HERE ;
Rising Tide:
The Impact of Dementia on Canadian Society
Executive Summary
http://www.alzheimer.ca/docs/RisingTide/AS%20Rising%20Tide-Executive%20Summary_Eng_FINAL_SecuredVersion.pdf
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
SEAC OCTOBER 2009
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
http://www.seac.gov.uk/pdf/hol-response091008.pdf
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...
snip...
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf
And NONE of this is relevant to BSE?
There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://web.archive.org/web/20010305223143/www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
also, see the increase of Alzheimer's from 1981 to 1986
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
see full text ;
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients Copyright © 2009 Published by Elsevier Inc.
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
----- Original Message -----
From: "Terry S. Singeltary Sr." To: Sent: Monday, October 12, 2009 9:47 AM Subject: [BSE-L] SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
snip...
. More specific examples of unanswered questions with health implications are:
. Will the eventual elimination of classical scrapie in the EU leave an ecological niche for other TSEs such as BSE or atypical scrapie?
. Is CWD transmissible to humans?
. Can a reliable ante mortem diagnostic blood test for vCJD be developed?
. What is the true prevalence of v CJD infection (as opposed to overt disease) in the UK?
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
--------------------------------------------------------------------------------
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
--------------------------------------------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
. Could cases of protease sensitive prionopathy (PSP) be missed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?
. Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?
SNIP...
FULL TEXT ;
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Monday, June 29, 2009 2:08 PM
Subject: [BSE-L] Beyond the prion principle
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
News and Views Nature 459, 924-925 (18 June 2009) doi:10.1038/459924a; Published online 17 June 2009
CELL BIOLOGY
Beyond the prion principle
Adriano Aguzzi
It seems that many misfolded proteins can act like prions - spreading disease by imparting their misshapen structure to normal cellular counterparts. But how common are bona fide prions really?
The protein-only hypothesis of prion propagation is steadily gaining ground. First envisaged by John Stanley Griffith1 and later formalized by Stanley Prusiner2, this theory proposes the existence of an infectious agent composed solely of protein. Three reports, two in Nature Cell Biology3,4 and one in The Journal of Cell Biology5, now contend that, far from being confined to the rare prion diseases, prion-like transmission of altered proteins may occur in several human diseases of the brain and other organs.
Prions are now accepted as causing the transmissible spongiform encephalopathies, which include scrapie in sheep, bovine spongiform encephalopathy (BSE, or mad cow disease) and its human variant Creutzfeldt-Jakob disease. The infectious prion particle is made up of PrPSc, a misfolded and aggregated version of a normal protein known as PrPC. Like the growth of crystals, PrPSc propagates by recruiting monomeric PrPC into its aggregates - a process that has been replicated in vitro6 and in transgenic mice7. The breakage of PrPSc aggregates represents the actual replicative event, as it multiplies the number of active seeds8.
Apart from prion diseases, the misfolding and aggregation of proteins into various harmful forms, which are collectively known as amyloid, causes a range of diseases of the nervous system and other organs. The clinical characteristics of amyloidoses, however, gave little reason to suspect a relationship to prion diseases. Hints of prion-like behaviour in amyloid have emerged from studies of Alzheimer's disease and Parkinson's disease. Alzheimer's disease had been suspected to be transmissible for some time: an early report9 of disease transmission to hamsters through white blood cells from people with Alzheimer's disease caused great consternation, but was never reproduced. Much more tantalizing evidence came from the discovery10,11 that aggregates of the amyloid-â (Aâ) peptide found in the brain of people with Alzheimer's disease could be transmitted to the brain of mice engineered to produce large amounts of the Aâ precursor protein APP. Another study12 has shown that healthy tissue grafted into the brain of people with Parkinson's disease acquires intracellular Lewy bodies - aggregates of the Parkinson's disease-associated protein á-synuclein. This suggests prion-like transmission of diseased protein from the recipient's brain to the grafted cells.
These findings10-12 raise a provocative question. If protein aggregation depends on the introduction of 'seeds' and on the availability of the monomeric precursor, and if, as has been suggested13, amyloid represents the primordial state of all proteins, wouldn't all proteins - under appropriate conditions - behave like prions in the presence of sufficient precursor? Acceptance of this concept is gaining momentum. For one thing, an increasing wealth of traits is being found in yeast, fungi and bacteria that can best be explained as prion-like phenomena (see table). And now, Ren and colleagues3 provide evidence for prion-like spread of polyglutamine (polyQ)- containing protein aggregates, which are similar to the aggregates found in Huntington's disease. They show that polyQ aggregates can be taken up from the outside by mammalian cells. Once in the cytosol, the polyQ aggregates can grow by recruiting endogenous polyQ. Clavaguera et al.4 report similar findings in a mouse model of tauopathy, a neurodegenerative disease caused by intraneuronal aggregation of the microtubule-associated tau protein. Injection of mutant human tau into the brain of mice overexpressing normal human tau transmitted tauopathy, with intracellular aggregation of previously normal tau and spread of aggregates to neighbouring regions of the brain. Notably, full-blown tauopathy was not induced in mice that did not express human tau. Assuming that tau pathology wasn't elicited by some indirect pathway (some mice overexpressing mutated human tau develop protein tangles even when exposed to un related amyloid aggregates14), this sequence of events is reminiscent of prions. Finally, Frost and colleagues5 show that extracellular tau aggregates can be taken up by cells in culture. Hence, tau can attack and penetrate cells from the outside, sporting predatory behaviour akin to that of prions.
Yet there is one crucial difference between actual prion diseases and diseases caused by other prion-like proteins (let's call them prionoids) described so far (see table). The behaviour of prions is entirely comparable to that of any other infectious agent: for instance, prions are transmissible between individuals and often across species, and can be assayed with classic microbiological techniques, including titration by bioassay. Accordingly, prion diseases were long thought to be caused by viruses, and BSE created a worldwide panic similar to that currently being provoked by influenza. By contrast, although prionoids can 'infect' neighbouring molecules and sometimes even neighbouring cells, they do not spread within communities or cause epidemics such as those seen with BSE.
So, should any amyloid deserve an upgrade to a bone fide prion status? Currently, amyloid A (AA) amyloidosis may be the most promising candidate for a truly infectious disease caused by a self-propagating protein other than PrPSc. AA amyloid consists of orderly aggregated fragments of the SAA protein, and its deposition damages many organs of the body. Seeds of AA amyloid can be excreted in faeces15, and can induce amyloidosis if taken up orally (at least in geese)16. Also, AA amyloid may be transmitted between mice by transfusion of white blood cells17. So, like entero viruses and, perhaps, sheep scrapie prions, AA amyloid seems to display all the elements of a complete infectious life cycle, including uptake, replication and release from its host.
There are intriguing evolutionary implications to the above findings. If prionoids are ubiquitous, why didn't evolution erect barriers to their pervasiveness? Maybe it is because the molecular transmissibility of aggregated states can sometimes be useful. Indeed, aggregation of the Sup35 protein, which leads to a prion-like phenomenon in yeast, may promote evolutionary adaptation by allowing yeast cells to temporarily activate DNA sequences that are normally untranslated18. Mammals have developed receptors for aggregates, and ironically PrPC may be one of them19, although these receptors have not been reported to mediate protective functions. Therefore, we shouldn't be shocked if instances of beneficial prionoids emerge in mammals as well. ¦
Adriano Aguzzi is at the Institute of Neuropathology, University Hospital of Zurich, CH-8091 Zurich, Switzerland. e-mail: adriano.aguzzi@usz.ch
1. Griffith, J. S. Nature 215, 1043-1044 (1967). 2. Prusiner, S. B. Science 216, 136-144 (1982). 3. Ren, P.-H. et al. Nature Cell Biol. 11, 219-225 (2009). 4. Clavaguera, F. et al. Nature Cell Biol. doi:10.1038/ncb1901 (2009). 5. Frost, B., Jacks, R. L. & Diamond, M. I. J. Biol. Chem. 284, 12845-12852 (2009). 6. Castilla, J., Saá, P., Hetz, C. & Soto, C. Cell 121, 195-206 (2005). 7. Sigurdson, C. J. et al. Proc. Natl Acad. Sci. USA 106, 304-309 (2009). 8. Aguzzi, A. & Polymenidou, M. Cell 116, 313-327 (2004). 9. Manuelidis, E. E. et al. Proc. Natl Acad. Sci. USA 85, 4898-4901 (1988). 10. Kane, M. D. et al. J. Neurosci. 20, 3606-3611 (2000). 11. Meyer-Luehmann, M. et al. Science 313, 1781-1784 (2006). 12. Li, J.-Y. et al. Nature Med. 14, 501-503 (2008). 13. Chiti, F. & Dobson, C. M. Annu. Rev. Biochem. 75, 333-366 (2006). 14. GÖtz, J., Chen, F., van Dorpe, J. & Nitsch, R. M. Science 293, 1491-1495 (2001). 15. Zhang, B. et al. Proc. Natl Acad. Sci. USA 105, 7263-7268 (2008). 16. Solomon, A. et al. Proc. Natl Acad. Sci. USA 104, 10998-11001 (2007). 17. Sponarova, J., NystrÖm, S. N. & Westermark, G. T. PLoS ONE 3, e3308 (2008). 18. True, H. L. & Lindquist, S. L. Nature 407, 477-483 (2000). 19. Laurén, J. et al. Nature 457, 1128-1132 (2009).
PRIONS AND POTENTIAL PRIONOIDS
Disease Protein Molecular transmissibility Infectious life cycle Prion diseases PrPSc Yes Yes Alzheimer's disease Amyloid-ß Yes Not shown Tauopathies Tau Yes Not shown Parkinson's disease a-Synuclein Host-to-graft Not shown AA amyloidosis Amyloid A Yes Possible Huntington's disease Polyglutamine Yes Not shown Phenotype Protein Molecular transmissibility Infectious life cycle Suppressed translational termination (yeast) Sup35 Yes Not shown Heterokaryon incompatibility (filamentous fungi) Het-s Yes Not shown Biofilm promotion (bacteria) CsgA Yes Not shown In humans and animals, infectious prion diseases are caused by PrPSc, which spreads by recruiting its monomeric precursor PrPC into aggregates. Aggregates then multiply by breakage, a process that is termed molecular transmissibility. Other proteins involved in disease and in phenotypes of fungi and bacteria, can also undergo self-sustaining aggregation, but none of these 'prionoid' proteins behaves like typical infectious agents, nor do any of them enact a complete infectious life cycle - with the possible exception of AA amyloid. Correction In the News & Views article "Immunology: Immunity's ancient arms" by Gary W. Litman and John P. Cannon (Nature 459, 784-786; 2009), the name of the fi rst author of the Nature paper under discussion was misspelt. The author's name is P. Guo, not Gou as published.
© 2009 Macmillan Publishers Limited. All rights reserved
http://www.nature.com/nature/journal/v459/n7249/full/459924a.html
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Saturday, January 2, 2010
Human Prion Diseases in the United States January 1, 2010 ***FINAL***
http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
Friday, January 01, 2010
Human Prion Diseases in the United States PART 1
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/human-prion-diseases-in-united-states.html
my comments to PLosone here ;
http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd
TSS
Saturday, November 14, 2009
Codistribution of Amyloid ß Plaques and Spongiform Degeneration in Familial Creutzfeldt-Jakob Disease With the E200K-129M Haplotype
Vol. 66 No. 10, October 2009
Codistribution of Amyloid ß Plaques and Spongiform Degeneration in Familial Creutzfeldt-Jakob Disease With the E200K-129M Haplotype
Nupur Ghoshal, MD, PhD; Ignazio Cali, MS; Richard Justin Perrin, MD, PhD; S. Andrew Josephson, MD; Ning Sun, MD, PhD; Pierluigi Gambetti, MD; John Carl Morris, MD
Arch Neurol. 2009;66(10):1240-1246.
Background Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Coexistent amyloid ß (Aß) plaques have been reported in some transmissible spongiform encephalopathies but to date have not been reported in familial CJD with the E200K mutation.
Objective To characterize a family with CJD in which Aß plaques codistribute with spongiform degeneration.
Design Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype.
Setting Alzheimer disease research center.
Participants Two generations of a family.
Main Outcome Measures Clinical, biochemical, and neuropathologic observations in 2 generations of a family.
Results In this kindred, 3 autopsied cases showed pathologic changes typical for the E200K-129M haplotype, including spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, 2 of these cases (ages 57 and 63 years) showed numerous Aß plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Aß plaques were present in the APOE 4 carrier but not in the APOE 4 noncarrier. Two additional cases exhibited incomplete penetrance, as they had no clinical evidence of CJD at death after age 80 years but had affected siblings and children.
Conclusions To our knowledge, this is the first description of Aß plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Aß formation and that Aß pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrPE200K may result in increased Aß deposition.
Author Affiliations: Department of Neurology and Alzheimer's Disease Research Center (Drs Ghoshal, Perrin, and Morris) and Division of Neuropathology, Department of Pathology and Immunology (Drs Perrin and Morris), Washington University School of Medicine, St Louis, Missouri; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio (Mr Cali and Dr Gambetti); Department of Neurology, University of California, San Francisco (Dr Josephson); and DuPage Neurological Associates, Willowbrook, Illinois (Dr Sun).
http://archneur.ama-assn.org/cgi/content/short/66/10/1240
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
SEAC OCTOBER 2009
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
http://www.seac.gov.uk/pdf/hol-response091008.pdf
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...
snip...
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf
And NONE of this is relevant to BSE?
There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://web.archive.org/web/20010305223143/www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
also, see the increase of Alzheimer's from 1981 to 1986
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
see full text ;
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
re-Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
TSS
Codistribution of Amyloid ß Plaques and Spongiform Degeneration in Familial Creutzfeldt-Jakob Disease With the E200K-129M Haplotype
Nupur Ghoshal, MD, PhD; Ignazio Cali, MS; Richard Justin Perrin, MD, PhD; S. Andrew Josephson, MD; Ning Sun, MD, PhD; Pierluigi Gambetti, MD; John Carl Morris, MD
Arch Neurol. 2009;66(10):1240-1246.
Background Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases. The E200K mutation in the prion protein (PrP) gene (PRNP) is the most frequent cause of familial CJD. Coexistent amyloid ß (Aß) plaques have been reported in some transmissible spongiform encephalopathies but to date have not been reported in familial CJD with the E200K mutation.
Objective To characterize a family with CJD in which Aß plaques codistribute with spongiform degeneration.
Design Clinicopathologic and molecular study of a family with CJD with the E200K-129M haplotype.
Setting Alzheimer disease research center.
Participants Two generations of a family.
Main Outcome Measures Clinical, biochemical, and neuropathologic observations in 2 generations of a family.
Results In this kindred, 3 autopsied cases showed pathologic changes typical for the E200K-129M haplotype, including spongiform degeneration, gliosis, neuronal loss, and PrP deposition. Moreover, 2 of these cases (ages 57 and 63 years) showed numerous Aß plaques codistributed with spongiform degeneration. APOE genotyping in 2 cases revealed that Aß plaques were present in the APOE 4 carrier but not in the APOE 4 noncarrier. Two additional cases exhibited incomplete penetrance, as they had no clinical evidence of CJD at death after age 80 years but had affected siblings and children.
Conclusions To our knowledge, this is the first description of Aß plaques in familial CJD with the E200K mutation. The codistribution of plaques and CJD-associated changes suggests that PrP plays a central role in Aß formation and that Aß pathology and prion disease likely in fluence each other. The kindred described herein provides support that PrPE200K may result in increased Aß deposition.
Author Affiliations: Department of Neurology and Alzheimer's Disease Research Center (Drs Ghoshal, Perrin, and Morris) and Division of Neuropathology, Department of Pathology and Immunology (Drs Perrin and Morris), Washington University School of Medicine, St Louis, Missouri; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio (Mr Cali and Dr Gambetti); Department of Neurology, University of California, San Francisco (Dr Josephson); and DuPage Neurological Associates, Willowbrook, Illinois (Dr Sun).
http://archneur.ama-assn.org/cgi/content/short/66/10/1240
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
http://betaamyloidcjd.blogspot.com/2009/10/involvement-of-dab1-in-app-processing.html
SEAC OCTOBER 2009
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
http://www.seac.gov.uk/pdf/hol-response091008.pdf
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://web.archive.org/web/20010305223440/www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...
snip...
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf
And NONE of this is relevant to BSE?
There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf
http://web.archive.org/web/20010305223234/www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://web.archive.org/web/20010305223143/www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
also, see the increase of Alzheimer's from 1981 to 1986
http://web.archive.org/web/20010305222847/www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
see full text ;
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures
http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html
re-Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease
http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
TSS
Saturday, October 31, 2009
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
Copyright © 2009 Published by Elsevier Inc.
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
References and further reading may be available for this article. To view references and further reading you must purchase this article.
R. Gavína, c, I. Ferrerb, c, , and J.A. del Ríoa, c, ,
aMolecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia and Department of Cell Biology, University of Barcelona, Baldiri Reixac 15-21, 08028 Barcelona, Spain
bInstitute of Neuropathology (INP), IDIBELL-Hospital Universitari de Bellvitge, Faculty of Medicine, University of Barcelona, 08907 Hospitalet de LLobregat, Barcelona, Spain
cCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
Received 27 March 2009; revised 5 October 2009; accepted 10 October 2009. Available online 21 October 2009.
Abstract Alzheimer's disease and prion pathologies (e.g., Creutzfeldt–Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of amyloid precursor protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in 17 cases of sporadic CJD (sCJD) post-mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrPsc types 1 and 2. One group with PrPsc type 1 showed increased Dab1 phosphorylation and lower ßCTF production with an absence of Aß deposition. The second sCJD group, which carried PrPsc type 2, showed lower levels of Dab1 phosphorylation and ßCTF production, and Aß deposition. Thus, the present observations suggest a correlation between Dab1 phosphorylation, Aß deposition and PrPsc type in sCJD.
Keywords: Prionopathies; Amyloid plaques; Alzheimer's disease; Dab1
Article Outline Introduction Patients and methods Cases PrP typing Codon 129 genotyping Immunoprecipitation and Western immunoblotting Densitometry and statistical processing Results Analysis of Dab1 phosphorylation revealed two groups of sCJD cases ßCTF production and Aß deposition in sCJD Correlation between codon 129 polymorphism with PrPsc type and Aß deposits in sCJD groups Discussion Acknowledgements References
Fig. 1. Patterns of PrPsc type 1 and type 2 (PK: proteinase K pre-treatment). Three examples of PrPsc processing are illustrated. Every sample is run in parallel with a negative control (lane 1), a typical case of PrPsc type 1 (lane 2), a typical case type 2 (lane 3) and the case problem (lane 4).
View Within Article
--------------------------------------------------------------------------------
Fig. 2. Example of Western blot determination of pDab1 (A and B) and total Dab1 protein levels (C and D) in sCJD cases. sCJD cases were categorized as described above. Protein samples from different groups of sCJD (first and second groups) are shown. (B) The densitometric results are shown. Each data item corresponding to a sCJD case is displayed in the histograms. In addition, the mean and SEM in each group is also shown. A significant increase in the pDab1/Dab1 ratio is observed in the first group of sCJD cases compared to the second sCJD group and controls. (C and D) Parallel determination of total Dab1 levels in the same sCJD protein samples. The increased phosphorylation of Dab1 in the first sCJD cases correlates with decreased levels of total protein. Each dot corresponds to a single case. Asterisks indicate significant differences between sCJD groups and controls in (B) and (D). p < 0.05; p < 0.01 (ANOVA test). View Within Article --------------------------------------------------------------------------------
Fig. 3. Example of Western blotting determination of ßCTF (A and B) in sCJD cases compared to controls. sCJD cases were categorized as described above. Decreased levels of ßCTF can be seen in the first sCJD group compared to controls. (B) Histograms showing the densitometric study as in Fig. 2. Each dot corresponds to a single case. Asterisks indicate significant differences between sCJD groups and controls. p < 0.05 (ANOVA test). View Within Article --------------------------------------------------------------------------------
Fig. 4. Double-Y graphs illustrating the densitometric results of pDab1/Dab1 ratio (left Y axis) and CTFß levels (blue right Y axis) for each case (X axis). Each dot/square corresponds to a single case. Values of pDab1/Dab1 (black squares) and CTFß (blue circles) have been linked with a line and the area (grey for pDab1/Dab1 and violet for CTFß) has been completed for each patient group. Notice the clear differences in the distribution of the grey and violet areas between the 1st and the 2nd group of sCJD cases and controls. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) View Within Article --------------------------------------------------------------------------------
Fig. 5. Low power photomicrographs illustrating examples of amyloid plaques in some of the sCJD cases used in the present study after Aß immunocytochemistry. (A) No plaques (score 0). (B) A few diffuse plaques (score +). (C) Many diffuse plaques, some neuritic plaques (score ++). See Results for details. Scale bar (A) = 500 µm pertains to (B) and (C). View Within Article --------------------------------------------------------------------------------
Table 1. Main clinical characteristics of sCJD and control cases in the present study. F: female; M: male; M: methionine; V: valine; PrP type: PrPsc type 1: lower band of glycosylated PrPsc of 21 kDa; type 2: lower band of glycosylated PrPsc of 10 kDa. Aß plaques: 0, no plaques; +, a few diffuse plaques; ++, many diffuse plaques and some neuritic plaques. View Within Article Corresponding authors. J.A. del Río is to be contacted at MCN lab Institute of Bioengineering of Catalonia Baldiri and Reixac 15-20, 08028 Barcelona, Spain. Fax: +34 934020183. I. Ferrer, Institut de Neuropatologia Servei Anatomia Patològica IDIBELL-Hospital Universitari de Bellvitge Facultat de Medicina Universitat de Barcelona Feixa LLarga sn, 08907 Hospitalet de LLobregat, Barcelona, Spain. Fax: +34 934035810.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNK-4XH5MGD-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=77549367eefa411de83e198f26401bcc
TSS
----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Monday, October 12, 2009 9:47 AM
Subject: [BSE-L] SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
snip...
. More specific examples of unanswered questions with health implications are:
. Will the eventual elimination of classical scrapie in the EU leave an ecological niche for other TSEs such as BSE or atypical scrapie?
. Is CWD transmissible to humans?
. Can a reliable ante mortem diagnostic blood test for vCJD be developed?
. What is the true prevalence of v CJD infection (as opposed to overt disease) in the UK?
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
--------------------------------------------------------------------------------
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
--------------------------------------------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
. Could cases of protease sensitive prionopathy (PSP) be missed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?
. Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?
SNIP...
FULL TEXT ;
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Monday, June 29, 2009 2:08 PM
Subject: [BSE-L] Beyond the prion principle
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
News and Views Nature 459, 924-925 (18 June 2009) doi:10.1038/459924a; Published online 17 June 2009
CELL BIOLOGY
Beyond the prion principle
Adriano Aguzzi
It seems that many misfolded proteins can act like prions - spreading disease by imparting their misshapen structure to normal cellular counterparts. But how common are bona fide prions really?
The protein-only hypothesis of prion propagation is steadily gaining ground. First envisaged by John Stanley Griffith1 and later formalized by Stanley Prusiner2, this theory proposes the existence of an infectious agent composed solely of protein. Three reports, two in Nature Cell Biology3,4 and one in The Journal of Cell Biology5, now contend that, far from being confined to the rare prion diseases, prion-like transmission of altered proteins may occur in several human diseases of the brain and other organs.
Prions are now accepted as causing the transmissible spongiform encephalopathies, which include scrapie in sheep, bovine spongiform encephalopathy (BSE, or mad cow disease) and its human variant Creutzfeldt-Jakob disease. The infectious prion particle is made up of PrPSc, a misfolded and aggregated version of a normal protein known as PrPC. Like the growth of crystals, PrPSc propagates by recruiting monomeric PrPC into its aggregates - a process that has been replicated in vitro6 and in transgenic mice7. The breakage of PrPSc aggregates represents the actual replicative event, as it multiplies the number of active seeds8.
Apart from prion diseases, the misfolding and aggregation of proteins into various harmful forms, which are collectively known as amyloid, causes a range of diseases of the nervous system and other organs. The clinical characteristics of amyloidoses, however, gave little reason to suspect a relationship to prion diseases. Hints of prion-like behaviour in amyloid have emerged from studies of Alzheimer's disease and Parkinson's disease. Alzheimer's disease had been suspected to be transmissible for some time: an early report9 of disease transmission to hamsters through white blood cells from people with Alzheimer's disease caused great consternation, but was never reproduced. Much more tantalizing evidence came from the discovery10,11 that aggregates of the amyloid-â (Aâ) peptide found in the brain of people with Alzheimer's disease could be transmitted to the brain of mice engineered to produce large amounts of the Aâ precursor protein APP. Another study12 has shown that healthy tissue grafted into the brain of people with Parkinson's disease acquires intracellular Lewy bodies - aggregates of the Parkinson's disease-associated protein á-synuclein. This suggests prion-like transmission of diseased protein from the recipient's brain to the grafted cells.
These findings10-12 raise a provocative question. If protein aggregation depends on the introduction of 'seeds' and on the availability of the monomeric precursor, and if, as has been suggested13, amyloid represents the primordial state of all proteins, wouldn't all proteins - under appropriate conditions - behave like prions in the presence of sufficient precursor? Acceptance of this concept is gaining momentum. For one thing, an increasing wealth of traits is being found in yeast, fungi and bacteria that can best be explained as prion-like phenomena (see table). And now, Ren and colleagues3 provide evidence for prion-like spread of polyglutamine (polyQ)- containing protein aggregates, which are similar to the aggregates found in Huntington's disease. They show that polyQ aggregates can be taken up from the outside by mammalian cells. Once in the cytosol, the polyQ aggregates can grow by recruiting endogenous polyQ. Clavaguera et al.4 report similar findings in a mouse model of tauopathy, a neurodegenerative disease caused by intraneuronal aggregation of the microtubule-associated tau protein. Injection of mutant human tau into the brain of mice overexpressing normal human tau transmitted tauopathy, with intracellular aggregation of previously normal tau and spread of aggregates to neighbouring regions of the brain. Notably, full-blown tauopathy was not induced in mice that did not express human tau. Assuming that tau pathology wasn't elicited by some indirect pathway (some mice overexpressing mutated human tau develop protein tangles even when exposed to un related amyloid aggregates14), this sequence of events is reminiscent of prions. Finally, Frost and colleagues5 show that extracellular tau aggregates can be taken up by cells in culture. Hence, tau can attack and penetrate cells from the outside, sporting predatory behaviour akin to that of prions.
Yet there is one crucial difference between actual prion diseases and diseases caused by other prion-like proteins (let's call them prionoids) described so far (see table). The behaviour of prions is entirely comparable to that of any other infectious agent: for instance, prions are transmissible between individuals and often across species, and can be assayed with classic microbiological techniques, including titration by bioassay. Accordingly, prion diseases were long thought to be caused by viruses, and BSE created a worldwide panic similar to that currently being provoked by influenza. By contrast, although prionoids can 'infect' neighbouring molecules and sometimes even neighbouring cells, they do not spread within communities or cause epidemics such as those seen with BSE.
So, should any amyloid deserve an upgrade to a bone fide prion status? Currently, amyloid A (AA) amyloidosis may be the most promising candidate for a truly infectious disease caused by a self-propagating protein other than PrPSc. AA amyloid consists of orderly aggregated fragments of the SAA protein, and its deposition damages many organs of the body. Seeds of AA amyloid can be excreted in faeces15, and can induce amyloidosis if taken up orally (at least in geese)16. Also, AA amyloid may be transmitted between mice by transfusion of white blood cells17. So, like entero viruses and, perhaps, sheep scrapie prions, AA amyloid seems to display all the elements of a complete infectious life cycle, including uptake, replication and release from its host.
There are intriguing evolutionary implications to the above findings. If prionoids are ubiquitous, why didn't evolution erect barriers to their pervasiveness? Maybe it is because the molecular transmissibility of aggregated states can sometimes be useful. Indeed, aggregation of the Sup35 protein, which leads to a prion-like phenomenon in yeast, may promote evolutionary adaptation by allowing yeast cells to temporarily activate DNA sequences that are normally untranslated18. Mammals have developed receptors for aggregates, and ironically PrPC may be one of them19, although these receptors have not been reported to mediate protective functions. Therefore, we shouldn't be shocked if instances of beneficial prionoids emerge in mammals as well. ¦
Adriano Aguzzi is at the Institute of Neuropathology, University Hospital of Zurich, CH-8091 Zurich, Switzerland. e-mail: adriano.aguzzi@usz.ch
1. Griffith, J. S. Nature 215, 1043-1044 (1967). 2. Prusiner, S. B. Science 216, 136-144 (1982). 3. Ren, P.-H. et al. Nature Cell Biol. 11, 219-225 (2009). 4. Clavaguera, F. et al. Nature Cell Biol. doi:10.1038/ncb1901 (2009). 5. Frost, B., Jacks, R. L. & Diamond, M. I. J. Biol. Chem. 284, 12845-12852 (2009). 6. Castilla, J., Saá, P., Hetz, C. & Soto, C. Cell 121, 195-206 (2005). 7. Sigurdson, C. J. et al. Proc. Natl Acad. Sci. USA 106, 304-309 (2009). 8. Aguzzi, A. & Polymenidou, M. Cell 116, 313-327 (2004). 9. Manuelidis, E. E. et al. Proc. Natl Acad. Sci. USA 85, 4898-4901 (1988). 10. Kane, M. D. et al. J. Neurosci. 20, 3606-3611 (2000). 11. Meyer-Luehmann, M. et al. Science 313, 1781-1784 (2006). 12. Li, J.-Y. et al. Nature Med. 14, 501-503 (2008). 13. Chiti, F. & Dobson, C. M. Annu. Rev. Biochem. 75, 333-366 (2006). 14. GÖtz, J., Chen, F., van Dorpe, J. & Nitsch, R. M. Science 293, 1491-1495 (2001). 15. Zhang, B. et al. Proc. Natl Acad. Sci. USA 105, 7263-7268 (2008). 16. Solomon, A. et al. Proc. Natl Acad. Sci. USA 104, 10998-11001 (2007). 17. Sponarova, J., NystrÖm, S. N. & Westermark, G. T. PLoS ONE 3, e3308 (2008). 18. True, H. L. & Lindquist, S. L. Nature 407, 477-483 (2000). 19. Laurén, J. et al. Nature 457, 1128-1132 (2009).
PRIONS AND POTENTIAL PRIONOIDS
Disease Protein Molecular transmissibility Infectious life cycle Prion diseases PrPSc Yes Yes Alzheimer's disease Amyloid-ß Yes Not shown Tauopathies Tau Yes Not shown Parkinson's disease a-Synuclein Host-to-graft Not shown AA amyloidosis Amyloid A Yes Possible Huntington's disease Polyglutamine Yes Not shown Phenotype Protein Molecular transmissibility Infectious life cycle Suppressed translational termination (yeast) Sup35 Yes Not shown Heterokaryon incompatibility (filamentous fungi) Het-s Yes Not shown Biofilm promotion (bacteria) CsgA Yes Not shown In humans and animals, infectious prion diseases are caused by PrPSc, which spreads by recruiting its monomeric precursor PrPC into aggregates. Aggregates then multiply by breakage, a process that is termed molecular transmissibility. Other proteins involved in disease and in phenotypes of fungi and bacteria, can also undergo self-sustaining aggregation, but none of these 'prionoid' proteins behaves like typical infectious agents, nor do any of them enact a complete infectious life cycle - with the possible exception of AA amyloid. Correction In the News & Views article "Immunology: Immunity's ancient arms" by Gary W. Litman and John P. Cannon (Nature 459, 784-786; 2009), the name of the fi rst author of the Nature paper under discussion was misspelt. The author's name is P. Guo, not Gou as published.
© 2009 Macmillan Publishers Limited. All rights reserved
http://www.nature.com/nature/journal/v459/n7249/full/459924a.html
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...
snip...
http://www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf
And NONE of this is relevant to BSE?
There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.
http://www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf
THE LINE TO TAKE.
http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
also, see the increase of Alzheimer's from 1981 to 1986
http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
Occasional PrP plaques are seen in cases of Alzheimer's Disease
snip...
full text;
http://www.bseinquiry.gov.uk/files/ws/s310.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
see full text ;
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
MAD COW DISEASE, AND U.S. BEEF TRADE
MAD COW DISEASE, CJD, TSE, SOUND SCIENCE, COMMERCE, AND SELLING YOUR SOUL TO THE DEVIL
http://usdameatexport.blogspot.com/2009/10/mad-cow-disease-and-us-beef-trade.html
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA
Involvement of Dab1 in APP processing and ß-amyloid deposition in sporadic Creutzfeldt–Jakob patients
References and further reading may be available for this article. To view references and further reading you must purchase this article.
R. Gavína, c, I. Ferrerb, c, , and J.A. del Ríoa, c, ,
aMolecular and Cellular Neurobiotechnology, Institute of Bioengineering of Catalonia and Department of Cell Biology, University of Barcelona, Baldiri Reixac 15-21, 08028 Barcelona, Spain
bInstitute of Neuropathology (INP), IDIBELL-Hospital Universitari de Bellvitge, Faculty of Medicine, University of Barcelona, 08907 Hospitalet de LLobregat, Barcelona, Spain
cCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
Received 27 March 2009; revised 5 October 2009; accepted 10 October 2009. Available online 21 October 2009.
Abstract Alzheimer's disease and prion pathologies (e.g., Creutzfeldt–Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of amyloid precursor protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in 17 cases of sporadic CJD (sCJD) post-mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrPsc types 1 and 2. One group with PrPsc type 1 showed increased Dab1 phosphorylation and lower ßCTF production with an absence of Aß deposition. The second sCJD group, which carried PrPsc type 2, showed lower levels of Dab1 phosphorylation and ßCTF production, and Aß deposition. Thus, the present observations suggest a correlation between Dab1 phosphorylation, Aß deposition and PrPsc type in sCJD.
Keywords: Prionopathies; Amyloid plaques; Alzheimer's disease; Dab1
Article Outline Introduction Patients and methods Cases PrP typing Codon 129 genotyping Immunoprecipitation and Western immunoblotting Densitometry and statistical processing Results Analysis of Dab1 phosphorylation revealed two groups of sCJD cases ßCTF production and Aß deposition in sCJD Correlation between codon 129 polymorphism with PrPsc type and Aß deposits in sCJD groups Discussion Acknowledgements References
Fig. 1. Patterns of PrPsc type 1 and type 2 (PK: proteinase K pre-treatment). Three examples of PrPsc processing are illustrated. Every sample is run in parallel with a negative control (lane 1), a typical case of PrPsc type 1 (lane 2), a typical case type 2 (lane 3) and the case problem (lane 4).
View Within Article
--------------------------------------------------------------------------------
Fig. 2. Example of Western blot determination of pDab1 (A and B) and total Dab1 protein levels (C and D) in sCJD cases. sCJD cases were categorized as described above. Protein samples from different groups of sCJD (first and second groups) are shown. (B) The densitometric results are shown. Each data item corresponding to a sCJD case is displayed in the histograms. In addition, the mean and SEM in each group is also shown. A significant increase in the pDab1/Dab1 ratio is observed in the first group of sCJD cases compared to the second sCJD group and controls. (C and D) Parallel determination of total Dab1 levels in the same sCJD protein samples. The increased phosphorylation of Dab1 in the first sCJD cases correlates with decreased levels of total protein. Each dot corresponds to a single case. Asterisks indicate significant differences between sCJD groups and controls in (B) and (D). p < 0.05; p < 0.01 (ANOVA test). View Within Article --------------------------------------------------------------------------------
Fig. 3. Example of Western blotting determination of ßCTF (A and B) in sCJD cases compared to controls. sCJD cases were categorized as described above. Decreased levels of ßCTF can be seen in the first sCJD group compared to controls. (B) Histograms showing the densitometric study as in Fig. 2. Each dot corresponds to a single case. Asterisks indicate significant differences between sCJD groups and controls. p < 0.05 (ANOVA test). View Within Article --------------------------------------------------------------------------------
Fig. 4. Double-Y graphs illustrating the densitometric results of pDab1/Dab1 ratio (left Y axis) and CTFß levels (blue right Y axis) for each case (X axis). Each dot/square corresponds to a single case. Values of pDab1/Dab1 (black squares) and CTFß (blue circles) have been linked with a line and the area (grey for pDab1/Dab1 and violet for CTFß) has been completed for each patient group. Notice the clear differences in the distribution of the grey and violet areas between the 1st and the 2nd group of sCJD cases and controls. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) View Within Article --------------------------------------------------------------------------------
Fig. 5. Low power photomicrographs illustrating examples of amyloid plaques in some of the sCJD cases used in the present study after Aß immunocytochemistry. (A) No plaques (score 0). (B) A few diffuse plaques (score +). (C) Many diffuse plaques, some neuritic plaques (score ++). See Results for details. Scale bar (A) = 500 µm pertains to (B) and (C). View Within Article --------------------------------------------------------------------------------
Table 1. Main clinical characteristics of sCJD and control cases in the present study. F: female; M: male; M: methionine; V: valine; PrP type: PrPsc type 1: lower band of glycosylated PrPsc of 21 kDa; type 2: lower band of glycosylated PrPsc of 10 kDa. Aß plaques: 0, no plaques; +, a few diffuse plaques; ++, many diffuse plaques and some neuritic plaques. View Within Article Corresponding authors. J.A. del Río is to be contacted at MCN lab Institute of Bioengineering of Catalonia Baldiri and Reixac 15-20, 08028 Barcelona, Spain. Fax: +34 934020183. I. Ferrer, Institut de Neuropatologia Servei Anatomia Patològica IDIBELL-Hospital Universitari de Bellvitge Facultat de Medicina Universitat de Barcelona Feixa LLarga sn, 08907 Hospitalet de LLobregat, Barcelona, Spain. Fax: +34 934035810.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WNK-4XH5MGD-1&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=77549367eefa411de83e198f26401bcc
TSS
----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Monday, October 12, 2009 9:47 AM
Subject: [BSE-L] SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
snip...
. More specific examples of unanswered questions with health implications are:
. Will the eventual elimination of classical scrapie in the EU leave an ecological niche for other TSEs such as BSE or atypical scrapie?
. Is CWD transmissible to humans?
. Can a reliable ante mortem diagnostic blood test for vCJD be developed?
. What is the true prevalence of v CJD infection (as opposed to overt disease) in the UK?
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
--------------------------------------------------------------------------------
. Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility
--------------------------------------------------------------------------------
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX
. Could cases of protease sensitive prionopathy (PSP) be missed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?
. Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?
SNIP...
FULL TEXT ;
Monday, October 12, 2009
SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE 8 October 2009
http://bse-atypical.blogspot.com/2009/10/seac-science-and-technology-committees.html
----- Original Message -----
From: "Terry S. Singeltary Sr."
To:
Sent: Monday, June 29, 2009 2:08 PM
Subject: [BSE-L] Beyond the prion principle
-------------------- BSE-L@LISTS.AEGEE.ORG --------------------
News and Views Nature 459, 924-925 (18 June 2009) doi:10.1038/459924a; Published online 17 June 2009
CELL BIOLOGY
Beyond the prion principle
Adriano Aguzzi
It seems that many misfolded proteins can act like prions - spreading disease by imparting their misshapen structure to normal cellular counterparts. But how common are bona fide prions really?
The protein-only hypothesis of prion propagation is steadily gaining ground. First envisaged by John Stanley Griffith1 and later formalized by Stanley Prusiner2, this theory proposes the existence of an infectious agent composed solely of protein. Three reports, two in Nature Cell Biology3,4 and one in The Journal of Cell Biology5, now contend that, far from being confined to the rare prion diseases, prion-like transmission of altered proteins may occur in several human diseases of the brain and other organs.
Prions are now accepted as causing the transmissible spongiform encephalopathies, which include scrapie in sheep, bovine spongiform encephalopathy (BSE, or mad cow disease) and its human variant Creutzfeldt-Jakob disease. The infectious prion particle is made up of PrPSc, a misfolded and aggregated version of a normal protein known as PrPC. Like the growth of crystals, PrPSc propagates by recruiting monomeric PrPC into its aggregates - a process that has been replicated in vitro6 and in transgenic mice7. The breakage of PrPSc aggregates represents the actual replicative event, as it multiplies the number of active seeds8.
Apart from prion diseases, the misfolding and aggregation of proteins into various harmful forms, which are collectively known as amyloid, causes a range of diseases of the nervous system and other organs. The clinical characteristics of amyloidoses, however, gave little reason to suspect a relationship to prion diseases. Hints of prion-like behaviour in amyloid have emerged from studies of Alzheimer's disease and Parkinson's disease. Alzheimer's disease had been suspected to be transmissible for some time: an early report9 of disease transmission to hamsters through white blood cells from people with Alzheimer's disease caused great consternation, but was never reproduced. Much more tantalizing evidence came from the discovery10,11 that aggregates of the amyloid-â (Aâ) peptide found in the brain of people with Alzheimer's disease could be transmitted to the brain of mice engineered to produce large amounts of the Aâ precursor protein APP. Another study12 has shown that healthy tissue grafted into the brain of people with Parkinson's disease acquires intracellular Lewy bodies - aggregates of the Parkinson's disease-associated protein á-synuclein. This suggests prion-like transmission of diseased protein from the recipient's brain to the grafted cells.
These findings10-12 raise a provocative question. If protein aggregation depends on the introduction of 'seeds' and on the availability of the monomeric precursor, and if, as has been suggested13, amyloid represents the primordial state of all proteins, wouldn't all proteins - under appropriate conditions - behave like prions in the presence of sufficient precursor? Acceptance of this concept is gaining momentum. For one thing, an increasing wealth of traits is being found in yeast, fungi and bacteria that can best be explained as prion-like phenomena (see table). And now, Ren and colleagues3 provide evidence for prion-like spread of polyglutamine (polyQ)- containing protein aggregates, which are similar to the aggregates found in Huntington's disease. They show that polyQ aggregates can be taken up from the outside by mammalian cells. Once in the cytosol, the polyQ aggregates can grow by recruiting endogenous polyQ. Clavaguera et al.4 report similar findings in a mouse model of tauopathy, a neurodegenerative disease caused by intraneuronal aggregation of the microtubule-associated tau protein. Injection of mutant human tau into the brain of mice overexpressing normal human tau transmitted tauopathy, with intracellular aggregation of previously normal tau and spread of aggregates to neighbouring regions of the brain. Notably, full-blown tauopathy was not induced in mice that did not express human tau. Assuming that tau pathology wasn't elicited by some indirect pathway (some mice overexpressing mutated human tau develop protein tangles even when exposed to un related amyloid aggregates14), this sequence of events is reminiscent of prions. Finally, Frost and colleagues5 show that extracellular tau aggregates can be taken up by cells in culture. Hence, tau can attack and penetrate cells from the outside, sporting predatory behaviour akin to that of prions.
Yet there is one crucial difference between actual prion diseases and diseases caused by other prion-like proteins (let's call them prionoids) described so far (see table). The behaviour of prions is entirely comparable to that of any other infectious agent: for instance, prions are transmissible between individuals and often across species, and can be assayed with classic microbiological techniques, including titration by bioassay. Accordingly, prion diseases were long thought to be caused by viruses, and BSE created a worldwide panic similar to that currently being provoked by influenza. By contrast, although prionoids can 'infect' neighbouring molecules and sometimes even neighbouring cells, they do not spread within communities or cause epidemics such as those seen with BSE.
So, should any amyloid deserve an upgrade to a bone fide prion status? Currently, amyloid A (AA) amyloidosis may be the most promising candidate for a truly infectious disease caused by a self-propagating protein other than PrPSc. AA amyloid consists of orderly aggregated fragments of the SAA protein, and its deposition damages many organs of the body. Seeds of AA amyloid can be excreted in faeces15, and can induce amyloidosis if taken up orally (at least in geese)16. Also, AA amyloid may be transmitted between mice by transfusion of white blood cells17. So, like entero viruses and, perhaps, sheep scrapie prions, AA amyloid seems to display all the elements of a complete infectious life cycle, including uptake, replication and release from its host.
There are intriguing evolutionary implications to the above findings. If prionoids are ubiquitous, why didn't evolution erect barriers to their pervasiveness? Maybe it is because the molecular transmissibility of aggregated states can sometimes be useful. Indeed, aggregation of the Sup35 protein, which leads to a prion-like phenomenon in yeast, may promote evolutionary adaptation by allowing yeast cells to temporarily activate DNA sequences that are normally untranslated18. Mammals have developed receptors for aggregates, and ironically PrPC may be one of them19, although these receptors have not been reported to mediate protective functions. Therefore, we shouldn't be shocked if instances of beneficial prionoids emerge in mammals as well. ¦
Adriano Aguzzi is at the Institute of Neuropathology, University Hospital of Zurich, CH-8091 Zurich, Switzerland. e-mail: adriano.aguzzi@usz.ch
1. Griffith, J. S. Nature 215, 1043-1044 (1967). 2. Prusiner, S. B. Science 216, 136-144 (1982). 3. Ren, P.-H. et al. Nature Cell Biol. 11, 219-225 (2009). 4. Clavaguera, F. et al. Nature Cell Biol. doi:10.1038/ncb1901 (2009). 5. Frost, B., Jacks, R. L. & Diamond, M. I. J. Biol. Chem. 284, 12845-12852 (2009). 6. Castilla, J., Saá, P., Hetz, C. & Soto, C. Cell 121, 195-206 (2005). 7. Sigurdson, C. J. et al. Proc. Natl Acad. Sci. USA 106, 304-309 (2009). 8. Aguzzi, A. & Polymenidou, M. Cell 116, 313-327 (2004). 9. Manuelidis, E. E. et al. Proc. Natl Acad. Sci. USA 85, 4898-4901 (1988). 10. Kane, M. D. et al. J. Neurosci. 20, 3606-3611 (2000). 11. Meyer-Luehmann, M. et al. Science 313, 1781-1784 (2006). 12. Li, J.-Y. et al. Nature Med. 14, 501-503 (2008). 13. Chiti, F. & Dobson, C. M. Annu. Rev. Biochem. 75, 333-366 (2006). 14. GÖtz, J., Chen, F., van Dorpe, J. & Nitsch, R. M. Science 293, 1491-1495 (2001). 15. Zhang, B. et al. Proc. Natl Acad. Sci. USA 105, 7263-7268 (2008). 16. Solomon, A. et al. Proc. Natl Acad. Sci. USA 104, 10998-11001 (2007). 17. Sponarova, J., NystrÖm, S. N. & Westermark, G. T. PLoS ONE 3, e3308 (2008). 18. True, H. L. & Lindquist, S. L. Nature 407, 477-483 (2000). 19. Laurén, J. et al. Nature 457, 1128-1132 (2009).
PRIONS AND POTENTIAL PRIONOIDS
Disease Protein Molecular transmissibility Infectious life cycle Prion diseases PrPSc Yes Yes Alzheimer's disease Amyloid-ß Yes Not shown Tauopathies Tau Yes Not shown Parkinson's disease a-Synuclein Host-to-graft Not shown AA amyloidosis Amyloid A Yes Possible Huntington's disease Polyglutamine Yes Not shown Phenotype Protein Molecular transmissibility Infectious life cycle Suppressed translational termination (yeast) Sup35 Yes Not shown Heterokaryon incompatibility (filamentous fungi) Het-s Yes Not shown Biofilm promotion (bacteria) CsgA Yes Not shown In humans and animals, infectious prion diseases are caused by PrPSc, which spreads by recruiting its monomeric precursor PrPC into aggregates. Aggregates then multiply by breakage, a process that is termed molecular transmissibility. Other proteins involved in disease and in phenotypes of fungi and bacteria, can also undergo self-sustaining aggregation, but none of these 'prionoid' proteins behaves like typical infectious agents, nor do any of them enact a complete infectious life cycle - with the possible exception of AA amyloid. Correction In the News & Views article "Immunology: Immunity's ancient arms" by Gary W. Litman and John P. Cannon (Nature 459, 784-786; 2009), the name of the fi rst author of the Nature paper under discussion was misspelt. The author's name is P. Guo, not Gou as published.
© 2009 Macmillan Publishers Limited. All rights reserved
http://www.nature.com/nature/journal/v459/n7249/full/459924a.html
Thursday, February 26, 2009
'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
Regarding Alzheimer's disease
(note the substantial increase on a yearly basis)
http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
snip...
The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...
snip...
http://www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf
And NONE of this is relevant to BSE?
There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.
http://www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf
THE LINE TO TAKE.
http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
also, see the increase of Alzheimer's from 1981 to 1986
http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf
Occasional PrP plaques are seen in cases of Alzheimer's Disease
snip...
full text;
http://www.bseinquiry.gov.uk/files/ws/s310.pdf
Tuesday, August 26, 2008
Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3
http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html
see full text ;
http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html
Alzheimer's and CJD
http://betaamyloidcjd.blogspot.com/
MAD COW DISEASE, AND U.S. BEEF TRADE
MAD COW DISEASE, CJD, TSE, SOUND SCIENCE, COMMERCE, AND SELLING YOUR SOUL TO THE DEVIL
http://usdameatexport.blogspot.com/2009/10/mad-cow-disease-and-us-beef-trade.html
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA
Monday, September 7, 2009
Scientists uncover new hereditary links to Alzheimer’s disease
Scientists uncover new hereditary links to Alzheimer’s disease
7 September 2009
Two genes which increase a person’s likelihood of developing the most common form of Alzheimer’s disease have been discovered in the largest-ever study of its kind into the illness. This international study, which received major funding from the Medical Research Council (MRC), is a significant step forward in understanding how Alzheimer’s develops and opens up new areas for further research into potential treatment and genetic screening.
Results from the research, which involved analysing the DNA from over 16,000 people over two years, show the genes CLU and PICALM can play a direct role in the risk of developing Alzheimer’s disease. Until now only one gene, APOE4, had been clearly identified as a potential risk factor. The Genome-Wide Association Study (GWAS) has emerged from the MRC new flagship research centre in Cardiff which is dedicated to genetic research into the disorders of the brain.
Lead author of the study, Professor Julie Williams, said:
“This research is changing our understanding of what might cause the common form of Alzheimer’s disease and could provide valuable new leads in the race to find treatments. If we can combat the detrimental effects of these two genes, we estimate it could reduce the chances of people developing Alzheimer's by almost 20%.”
Sir Leszek Borysiewicz, Chief Executive of the Medical Research Council, said: “Funding work on neurodegenerative diseases is priority for us and MRC investment in this kind of innovative research is crucial in piecing together the Alzheimer’s puzzle. This study is a huge step towards achieving an earlier diagnosis of Alzheimer’s and improving the lives of the many people affected by the disease."
Dr Marie Janson, Director of Development at the Alzheimer’s Research Trust, said:
“These unprecedented findings are the result of collaborations led by funders and scientists alike. Charities including the Alzheimer’s Research Trust and Wellcome Trust enhanced the MRC’s immense contribution to this work, while scientists throughout the UK and around the world shared data, ideas and more to make the study possible. This opens up multiple avenues that could lead to the development of new treatments for this devastating disease.”
The Medical Research Council invested £1.74 million in the programme of research, alongside major funding from the Wellcome Trust, the Welsh Assembly Government and the Alzheimer’s Research Trust, among others.
2
Data from the GWAS research was shared with a further French-led study, which has revealed compelling evidence for a third gene associated with Alzheimer’s called CR1.
Notes:
1. The Medical Research Council is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. www.mrc.ac.uk
2. The Genome-Wide Association Study (GWAS) identifies variants at CLU and PICALM associated with Alzheimer’s disease’ by Williams et al is published in Nature Genetics.
3. Both CLU and PICALM highlight new pathways that lead to Alzheimer's disease. The CLU gene produces clusterin which normally acts to protect the brain in a variety of ways. Variation in this gene could remove this protection and contribute to Alzheimer's development. PICALM is important at synapses - connections between brain cells - and is involved in the transport of molecules into and inside of nerve cells, helping form memories and other brain functions. We know that the health of synapses is closely related to memory performance in Alzheimer's disease, thus changes in genes which affect synapses are likely to have a direct effect on disease development.
4. Professor Julie Williams is Professor of Neuropsychology Genetics at the Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics based at the University of Cardiff. For more information about the new flagship centre in Cardiff visit:
http://www.mrc.ac.uk/Newspublications/News/MRC006193
5. Alzheimer's disease is the most common cause of dementia, affecting around 417,000 people in the UK. Alzheimer's disease, first described by the German neurologist Alois Alzheimer, is a physical disease affecting the brain. During the course of the disease, 'plaques' and 'tangles' develop in the structure of the brain, leading to the death of brain cells. People with Alzheimer's also have a shortage of some important chemicals in their brains. These chemicals are involved with the transmission of messages within the brain
6. Following the establishment of a collaborative consortium between Europe and the United States, the investigation involved researchers from universities in Cardiff, London, Cambridge, Nottingham, Southampton, Manchester, Oxford, Bristol and Belfast, as well as Irish, German, Belgian, Greek and American institutions.
Press contact: 020 7637 6011
press.office@headoffice.mrc.ac.uk
http://www.mrc.ac.uk/consumption/groups/public/documents/content/mrc006341.pdf
SEE ALZHEIMER'S AND CJD
http://betaamyloidcjd.blogspot.com/
TSS
7 September 2009
Two genes which increase a person’s likelihood of developing the most common form of Alzheimer’s disease have been discovered in the largest-ever study of its kind into the illness. This international study, which received major funding from the Medical Research Council (MRC), is a significant step forward in understanding how Alzheimer’s develops and opens up new areas for further research into potential treatment and genetic screening.
Results from the research, which involved analysing the DNA from over 16,000 people over two years, show the genes CLU and PICALM can play a direct role in the risk of developing Alzheimer’s disease. Until now only one gene, APOE4, had been clearly identified as a potential risk factor. The Genome-Wide Association Study (GWAS) has emerged from the MRC new flagship research centre in Cardiff which is dedicated to genetic research into the disorders of the brain.
Lead author of the study, Professor Julie Williams, said:
“This research is changing our understanding of what might cause the common form of Alzheimer’s disease and could provide valuable new leads in the race to find treatments. If we can combat the detrimental effects of these two genes, we estimate it could reduce the chances of people developing Alzheimer's by almost 20%.”
Sir Leszek Borysiewicz, Chief Executive of the Medical Research Council, said: “Funding work on neurodegenerative diseases is priority for us and MRC investment in this kind of innovative research is crucial in piecing together the Alzheimer’s puzzle. This study is a huge step towards achieving an earlier diagnosis of Alzheimer’s and improving the lives of the many people affected by the disease."
Dr Marie Janson, Director of Development at the Alzheimer’s Research Trust, said:
“These unprecedented findings are the result of collaborations led by funders and scientists alike. Charities including the Alzheimer’s Research Trust and Wellcome Trust enhanced the MRC’s immense contribution to this work, while scientists throughout the UK and around the world shared data, ideas and more to make the study possible. This opens up multiple avenues that could lead to the development of new treatments for this devastating disease.”
The Medical Research Council invested £1.74 million in the programme of research, alongside major funding from the Wellcome Trust, the Welsh Assembly Government and the Alzheimer’s Research Trust, among others.
2
Data from the GWAS research was shared with a further French-led study, which has revealed compelling evidence for a third gene associated with Alzheimer’s called CR1.
Notes:
1. The Medical Research Council is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. www.mrc.ac.uk
2. The Genome-Wide Association Study (GWAS) identifies variants at CLU and PICALM associated with Alzheimer’s disease’ by Williams et al is published in Nature Genetics.
3. Both CLU and PICALM highlight new pathways that lead to Alzheimer's disease. The CLU gene produces clusterin which normally acts to protect the brain in a variety of ways. Variation in this gene could remove this protection and contribute to Alzheimer's development. PICALM is important at synapses - connections between brain cells - and is involved in the transport of molecules into and inside of nerve cells, helping form memories and other brain functions. We know that the health of synapses is closely related to memory performance in Alzheimer's disease, thus changes in genes which affect synapses are likely to have a direct effect on disease development.
4. Professor Julie Williams is Professor of Neuropsychology Genetics at the Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics based at the University of Cardiff. For more information about the new flagship centre in Cardiff visit:
http://www.mrc.ac.uk/Newspublications/News/MRC006193
5. Alzheimer's disease is the most common cause of dementia, affecting around 417,000 people in the UK. Alzheimer's disease, first described by the German neurologist Alois Alzheimer, is a physical disease affecting the brain. During the course of the disease, 'plaques' and 'tangles' develop in the structure of the brain, leading to the death of brain cells. People with Alzheimer's also have a shortage of some important chemicals in their brains. These chemicals are involved with the transmission of messages within the brain
6. Following the establishment of a collaborative consortium between Europe and the United States, the investigation involved researchers from universities in Cardiff, London, Cambridge, Nottingham, Southampton, Manchester, Oxford, Bristol and Belfast, as well as Irish, German, Belgian, Greek and American institutions.
Press contact: 020 7637 6011
press.office@headoffice.mrc.ac.uk
http://www.mrc.ac.uk/consumption/groups/public/documents/content/mrc006341.pdf
SEE ALZHEIMER'S AND CJD
http://betaamyloidcjd.blogspot.com/
TSS
Subscribe to:
Posts (Atom)