Alzheimer's and CJD: TRANSMISSIBLE

Mice injected with Alzheimer's cast new light on dementia

Alok Jha guardian.co.uk, Sunday 7 June 2009 19.11 BST

Scientists have found that harmful tangles of proteins that cause diseases such as Alzheimer's can be transmitted from one brain to another, spreading and causing damage after being injected into the brains of mice. The researchers stressed, however, that Alzheimer's was not contagious and said it could not be caught, for example, through blood transfusions.

Alzheimer's and similar neurodegenerative diseases can be caused by the build-up in the brain of tangled masses of a type of protein called tau. They destroy brain function and, when they damage large amounts of tissue, can lead to dementia.

In experiments on mice, researchers found that the tau tangles could spread in the brain, as though they were an infectious agent, and be injected in tissue from the brain of an affected mouse into the brain of a healthy one. The research is published tomorrow in the journal Nature Cell Biology, and gives scientists a much better idea of how to target therapies for neurodegenerative diseases.

Michel Goedert of the Medical Research Council's Laboratory of Molecular Biology in Cambridge, who took part in the study, said the work opened up new avenues in understanding and allowing scientists to experiment with the causes of dementia.

"This research in mice does not show that tau pathology is contagious or it can spread easily from mouse to mouse - what it has revealed is how tau tangles spread within brain tissues of individual mice," he said. "It suggests that tangles of proteins that build up in the brain to cause symptoms could have some contagious properties within brain tissue but not between mice that haven't been injected with tissue from another mouse and certainly not between people." Though they are also bits of protein, tau tangles do transmit in the same way as prions, the proteins that cause diseases such as vCJD and mad cow disease by destroying brain tissue, because they cannot be passed easily between individuals.

Rebecca Wood, chief executive of the Alzheimer's Research Trust, said: "This greater understanding of how tangles spread in Alzheimer's may lead to new ways of stopping them and defeating the disease." Abnormal tangles build up in the brain during Alzheimer's and other diseases of the brain. It's not clear how that happens - but it is clear that Alzheimer's itself is not contagious. We desperately need more research like this to find answers to dementia, a cruel condition that affects 700,000 people in the UK."

There is still much unknown about the changes in tau protein that lead to tangle formation in humans and, eventually, widespread brain cell death. But

Susanne Sorensen, head of research at the Alzheimer's Society, said: "Each new piece of knowledge helps build a better picture and takes us closer to the point where we can stop loss of brain tissue and dementia for good."

http://www.guardian.co.uk/science/2009/jun/07/alzheimers-transmission-mice-dementia-research

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.

93/01.05/4.1

http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf

Regarding Alzheimer's disease

(note the substantial increase on a yearly basis)

http://collections.europarchive.org/tna/20080103032314/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://collections.europarchive.org/tna/20080102220341/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://collections.europarchive.org/tna/20080102223915/http://www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf

???

http://collections.europarchive.org/tna/20080102224230/http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf

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

also, see the increase of Alzheimer's from 1981 to 1986

http://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

Wednesday, April 14, 2010

Food Combination and Alzheimer Disease Risk A Protective Diet

http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html

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 ain 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

don't think dogs can't get a TSE prion disease either ??? don't bet on it, it's already happened ;

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

http://betaamyloidcjd.blogspot.com/

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Alzheimer's and CJD

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Thursday, October 28, 2010

Alzheimer's Disease Constituent Response From Senator Kay Bailey Hutchison

Sunday, June 7, 2009

ALZHEIMER'S DISEASE IS TRANSMISSIBLE