Sunday, February 5, 2012

Cellular prion protein participates in amyloid-β transcytosis across the blood–brain barrier

Brief Communication

Journal of Cerebral Blood Flow & Metabolism , (1 February 2012) | doi:10.1038/jcbfm.2012.7

Cellular prion protein participates in amyloid-β transcytosis across the blood–brain barrier

Thorsten Pflanzner, Benjamin Petsch, Bettina André-Dohmen, Andreas Müller-Schiffmann, Sabrina Tschickardt, Sascha Weggen, Lothar Stitz, Carsten Korth and Claus U Pietrzik



The blood–brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [125I]-Aβ1−40 transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric Aβ1−40 binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD.
http://www.nature.com/jcbfm/journal/vaop/ncurrent/full/jcbfm20127a.html
Supplementary Information (doc 343K) see below ;

SUPPLEMENTARY INFORMATION

Supplementary methods

Generation of monoclonal antibody 51.2

Monoclonal antibody 51.2 was generated by immunization of Prnp0/0 mice with SDS-purified sodium phosphotungstic acid (NaPTA)-precipitated Rocky mountain laboratory (RML) strain scrapie brain material (Bueler et al 1992). 250 µl of a 10 % brain homogenate of terminally RML-infected CD1 mice, were precipitated with NaPTA as described elsewhere (Wadsworth et al 2001). The resulting pellet was mixed with SDS-PAGE loading puffer (Roti-load 1, Carl Roth, Karlsruhe, Germany) heated at 95 °C for 10 minutes and separated on a SDS-gel. Gel slices corresponding to molecular weight from 16 to 30 kDa were cut from the gel and homogenized using mortar and liquid nitrogen. Mice were immunized using an equivalent to 250 µl of 10 % homogenate subcutaneously per mouse. Mice were immunized 4-times s.c. and i.p.boostered four days prior to fusion of spleen cells of immunized mice to X63.Ag8.8163 cells as described before by Kohler and Milstein (Kohler and Milstein 1975). Hybridoma supernatants were screened by ELISA using recombinant prion protein expressed in E. coli.
Flow cytometric analysis
Binding of monoclonal antibody 51.2 to prion protein on cell surface was determined using neuroblastoma cell lines Bos2 or ScN2a (Bosque and Prusiner 2000) as described before (Petsch et al 2011). The prion protein specific monoclonal antibody W226 was used as positive control (Petsch et al 2011).
Primary mouse brain capillary endothelial cell (pMBCEC) transwell transport model
Meninges-free forebrains of 6-10 week old C57Bl6 wild-type (WT) and cellular prion protein (PrPc) knock out (KO; Prnp0/0) mice were pooled, mechanically dissociated and, subsequently enzymatically digested (Bueler et al 1992; Pflanzner et al 2011). Endothelial capillaries were separated on a 33% continuous Percoll (GE Healthcare, Munich, Germany) gradient, collected and plated in 24 well transwell dishes (membrane pore size 0.4 µm and growth surface area 31.2 mm2; Greiner Bio-One, Frickenhausen, Germany) coated with collagen IV/fibronectin (Sigma, Schnelldorf, Germany). Hence, the lower abluminal compartment represents the brain side and the upper luminal compartment the blood side. Cultures were maintained in DMEM supplemented with 20% plasma-derived bovine serum (PDS; First Link, Birmingham, UK), 100 U/ml penicillin and 100 µg/ml streptomycin, 2 mM L-glutamine (all from Gibco, Darmstadt, Germany) and 1 ng/ml basic fibroblast growth factor (R&D Sytems, Wiesbaden, Germany) at 37 °C and 5% CO2. After reaching confluence on day 5, the culture medium was removed and serum-free DMEM/Ham’s F12 (Gibco) medium, containing 1 mM L-glutamine, 100 U/ml penicillin, 100 µg/ml streptomycin and 550 nM hydrocortisone (HC; Sigma) was added to induce high transendothelial electrical resistance for 24 hours.
Co-immunoprecipitation, sodium dodecylsulfate-polyacrylamide gel and Western blot analysis
Expression of PrPc and low density lipoprotein receptor-related protein 1 (LRP1) was analyzed in freshly isolated pMBCECs, LRP1-deficient mouse embryonic fibroblasts (MEFs) and brain homogenates of PrPc WT and KO mice in VRL buffer (50 mM HEPES pH 7.5, 100 mM KAc, 5 mM MgCl2, 250 mM sucrose and 1% Triton X-100). Cells were lyzed in NP-40 buffer containing proteinase inhibitors (complete; Roche Applied Science, Mannheim, Germany) and protein concentration was determined by the BCA method (Pierce, Bonn, Germany). For pMBCECs, 98 µg protein representing all capillaries derived from 10 mice, were analyzed.
LRP1 was immunoprecipitated from pMBCEC and LRP1-deficient chinese hamster ovary cell (13-5-1) lysates with rabbit polyclonal anti-LRP1 (1704) antibody at a final dilution of 1:100 in the presence of Protein A Agarose beads (Invitrogen, Darmstadt, Germany) (Pietrzik et al 2002). Prior to immunoprecipitation, 13-5-1 cells were transiently transfected with human PrPc in pcDNA3.1 for 48 hours with FuGeneHD (Roche) transfection reagent according to manufacturer instructions.
Proteins were separated on a 12% tris-glycine gel under denaturing and reducing conditions and transferred to a PVDF membrane (Millipore, Schwalbach, Germany) for 2 hours at 70 V on ice. Membrane was blocked in Tris-buffered saline containing 0.1% Tween 20 (v/v) and 5% milk (w/v). Mouse monoclonal anti-PrPc (1 µg/ml; W226) and anti-α-tubulin (clone DM1A 1:5000; Sigma), rabbit polyclonal anti-LRP1 (1:10000; 1704) and anti-actin (1:1000; Sigma) were used as primary antibodies (Petsch et al 2011). Secondary goat-anti-mouse and goat-anti-rabbitt IgGs linked to horseradish peroxidase (dilution 1:10000; The Jackson Laboratory, Sulzfeld, Germany) were used to visualize protein bands by ECL (Millipore) reagent.

Supplementary results
Generation and binding characteristics of monoclonal antibody 51.2
The monoclonal antibody 51.2 was generated by immunization of Prnp0/0mice using NaPTA-precipitated pathological prion protein that was further separated by SDS-PAGE as described under supplementary methods (Bueler et al 1992). Monoclonal antibody 51.2 reacted with recombinant prion protein in ELISA (data not shown) and detected prion protein in western blotting using brain homogenate of scrapie infected (RML) or control mice (Supplementary figure 1a). Both cellular and pathological prion protein were recognized by the monoclonal antibody 51.2, displaying the characteristic banding pattern in western blotting, staining the three glycoforms (non-, mono- and di-glycosylated prion protein) and C2-fragment of the prion protein (Supplementary figure 1a) (Chen et al 1995). The characteristic “down-shift” of the three glycoforms of the pathological prion protein PrPsc after proteinase K digestion strongly supports the specificity of the monoclonal antibody 51.2 for the prion protein.
The epitope of monoclonal antibody 51.2 was determined using a membrane-bound peptide library as described before (Petsch et al 2011), and identified to be a linear epitope located between amino acids (aa) 93-101 comprising the amino acid sequence GGTHNQWNK of the prion protein (numbering of aa referring to the sequence of hamster prion protein). Interestingly, the 51.2 epitope overlaps with the epitope of the monoclonal antibody 6D11 ( aa 93-110), an antibody that has previously been described to block the interaction between Aβ42 oligomers and PrPc (Lauren et al 2009).
The binding of monoclonal antibody 51.2 to prion protein on the surface of cells was demonstrated using Bos2 and ScN2a cells (Supplementary figure 1b (Bos 2) and 1c (ScN2a cells)). Unstained cells or cells stained with secondary antibody alone did not result in positive signals. In contrast thereto, cells stained with monoclonal antibody 51.2 or prion protein specific control antibody W226 both resulted in staining of distinct populations of cells (Petsch et al 2011), both in Bos2 or ScN2a cells, demonstrating the capacity of monoclonal antibody 51.2 to bind to the prion protein on the surface of both infected and non-infected prion protein expressing cells.

Supplementary references
Bosque PJ, Prusiner SB (2000) Cultured cell sublines highly susceptible to prion infection. J Virol 74:4377-86
Bueler H, Fischer M, Lang Y, Bluethmann H, Lipp HP, DeArmond SJ, Prusiner SB, Aguet M, Weissmann C (1992) Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature 356:577-82
Chen SG, Teplow DB, Parchi P, Teller JK, Gambetti P, Autilio-Gambetti L (1995) Truncated forms of the human prion protein in normal brain and in prion diseases. J Biol Chem 270:19173-80
Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495-7
Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457:1128-32
Petsch B, Muller-Schiffmann A, Lehle A, Zirdum E, Prikulis I, Kuhn F, Raeber AJ, Ironside JW, Korth C, Stitz L (2011) Biological effects and use of PrPSc- and PrP-specific antibodies generated by immunization with purified full-length native mouse prions. J Virol 85:4538-46
Pflanzner T, Janko MC, Andre-Dohmen B, Reuss S, Weggen S, Roebroek AJ, Kuhlmann CR, Pietrzik CU (2011) LRP1 mediates bidirectional transcytosis of amyloid-beta across the blood-brain barrier. Neurobiol Aging 32:2323 e1- e11
Pietrzik CU, Busse T, Merriam DE, Weggen S, Koo EH (2002) The cytoplasmic domain of the LDL receptor-related protein regulates multiple steps in APP processing. Embo J 21:5691-700
Wadsworth JD, Joiner S, Hill AF, Campbell TA, Desbruslais M, Luthert PJ, Collinge J (2001) Tissue distribution of protease resistant prion protein in variant Creutzfeldt-Jakob disease using a highly sensitive immunoblotting assay. Lancet 358:171-80
Titles and legends to supplementary figures
Supplementary Figure 1 The monoclonal antibody (Ab) 51.2 recognizes the prion protein in western blotting and on the surface of neuroblastoma cells.(a) Brain homogenate of scrapie infected (RML: +) and control mice (RML: -) were separated by SDS-PAGE and subsequently used for western blotting. Samples of brain homogenates were digested with proteinase K (PK: +) to eliminate cellular prion protein PrPc. Banding pattern in undigested scrapie-infected brain homogenate corresponds to di-, mono-, non-glycosylated or C2-fragment of prion protein (Chen et al 1995). (b and c) Binding of monoclonal antibody 51.2 to prion protein on the surface of neuroblastoma cell line Bos2 (b) or ScN2a (c) by flow cytometric analysis. Surface staining of PrPc by mAb 51.2 is demonstrated by shift of negative population in negative controls (unstained and secondary antibody (sec control)) from lower left quadrant to upper left quadrant using mAb 51.2 or W226.
Supplementary figure 1
snip...end...TSS
http://www.nature.com/jcbfm/journal/vaop/ncurrent/full/jcbfm20127a.html



Wednesday, January 18, 2012


Government seeking $1T campaign against Alzheimer's


http://betaamyloidcjd.blogspot.com/2012/01/government-seeking-1t-campaign-against.html




TSS

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Wednesday, January 18, 2012

Government seeking $1T campaign against Alzheimer's

January 17, 2012 12:57 PM
 
 
 
Gov't wants Alzheimer's treatment that works by 2025

By CBS News Staff

(CBS/AP) By 2025, Scientists need to develop an effective treatment for Alzheimer's disease, says the U.S. Government. The Obama administration announced today a plan for the government to step in and help find a way to treat and prevent the deadly neurological disease.

PICTURES: Alzheimer's disease: 7 things that raise your risk

The announcement of the nation's first National Alzheimer's Plan is not a moment too soon. An estimated 5.4 million Americans currently have the disease, but research suggests that by 2050, that number may nearly triple to 16 million Americans living with the disease - costing $1 trillion in medical and nursing home expenditures.

The government is setting what it calls an ambitious goal for progress in tackling the disease. The plan doesn't provide details of how to fund the necessary research to meet that target date. Today's treatments only temporarily ease some dementia symptoms, and work to find better ones has been frustratingly slow.
 
 
 
A committee of Alzheimer's experts begins a two-day meeting Tuesday to help advise the government on how to finalize the plan.

Families have been "reminding us of the enormity of our task, perhaps most important the meaningfulness of it," said the committee's chair, Dr. Ron Petersen, an Alzheimer's specialist at the Mayo Clinic.

But hanging over the meeting is the reality of a budget crunch. It's not clear how much money the federal government will be able to devote to Alzheimer's, and states have seen their Alzheimer's budgets cut.

"We're not going to fix this without substantial resources," said David Hoffman of the New York State Department of Health, who oversees that state's Alzheimer's programs. "In New York, we're hanging on by our nails."

Alzheimer's disease is the sixth leading cause of death in the U.S., according to the CDC's latest report, taking more than 83,000 lives this past year.
 
 
 
The national plan is supposed to tackle both the medical and social aspects of dementia, and advocacy groups had urged that it set a deadline for progress.

One of the draft's goals it to improve the timely diagnosis for the disease. A recent report found as many as half of today's Alzheimer's sufferers haven't been formally diagnosed, in part because of stigma and the belief that nothing can be done. Symptomatic treatment aside, a diagnosis lets families plan, and catching the disease earlier would be crucial if scientists ever find ways to slow the disease's progress.

Another goal of the plan is to improve support and training for families so they know what resources are available for patients and what to expect as dementia worsens. A caregiver-training program in New York has shown that families taught how to handle common dementia problems, and given support, are able to keep their loved ones at home for longer. Hoffman said such training programs are far cheaper than nursing homes.

Alzheimer's sufferers gradually lose the ability to do the simplest activities of daily life and can survive that way for a decade or more. A recent study suggests memory loss from aging could start as early as 45, HealthPop reported.

In meetings around the country last summer and fall, families urged federal health officials to make sure the national plan addresses how to help patients live their last years at home without ruining their caregivers' own health and finances.

According to a study in the Lancet Neurology, simple lifestyle changes may go a long way in staving off Alzheimer's disease. The study found that by reducing risk factors - such as obesity and blood pressure - by 25 percent, it could mean 3 million fewer cases of Alzheimer's worldwide, HealthPop reported.

Here are 7 ways to reduce your risk for Alzheimer's disease:

 
 
 
Government seeking $1T campaign against Alzheimer's



Greetings,
 
 
 
I was so saddened by this video, and then I became angry as hell. our family has been hit with not only Alzheimer’s, but also the Heidenhain Variant Creutzfeldt Jakob disease. These Transmissible Spongiform Encephalopathies have been spreading for decades, and thanks to Corporate interest, they were all simply lied about and or just swept under the rug. now look where we are, and yes, I believe that science has shown that Alzheimer’s disease is transmissible. NOW, think why the explosion of Alzheimer’s disease victims?


IATROGENIC !!!
 
 
 
Ann N Y Acad Sci. 1982;396:131-43.
 
 
 
Alzheimer's disease and transmissible virus dementia (Creutzfeldt-Jakob disease).

 
Brown P, Salazar AM, Gibbs CJ Jr, Gajdusek DC.

Abstract
 
 
 
Ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for AD and the spongiform virus encephalopathies. However, the crux of the comparison rests squarely on results of attempts to transmit AD to experimental animals, and these results have not as yet validated a common etiology. Investigations of the biologic similarities between AD and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoculated animals will be continued in the hope that incubation periods for AD may be even longer than those of CJD.


 
 
 
 
CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

Dr McGovern 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 p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative 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
 
 
 
 
 
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

1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognized 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 emphasizes 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
 
 
 
BSE101/1 0137

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.

JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832

121/YdeStss
 
 
 
92/11.4/1.2
 
 
 
 
 
 
Tuesday, October 4, 2011

De novo induction of amyloid-β deposition in vivo
 
 
 
Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120


 
 
 
Wednesday, September 21, 2011
 
 
 
PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)

Researchers’ Discovery May Revolutionize Treatment of ALS
 
 
 


Friday, August 13, 2010
 
 
 
Creutzfeldt-Jakob disease (CJD) biannual update 13 August 2010 UK Iatrogenic CJD Incidents Report
 
 
 
 
 
 
Tuesday, March 29, 2011

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE

 
 
 
 
 
 
 
 
 
 
 
 
TSS
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Tuesday, October 4, 2011

De novo induction of amyloid-β deposition in vivo


Molecular Psychiatry advance online publication 4 October 2011; doi: 10.1038/mp.2011.120

De novo induction of amyloid-β deposition in vivo



R Morales1,2, C Duran-Aniotz1,3, J Castilla2,4, L D Estrada2,5 and C Soto1,2

  1. 1Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX, USA
  2. 2University of Texas Medical Branch at Galveston, Galveston, TX, USA
  3. 3Universidad de Los Andes, Facultad de Medicina. Av. San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile
  4. 4CIC bioGUNE, Parque Tecnologico de Biskaia, Ed 800, 48160 Derio and IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain



Correspondence: Dr C Soto, Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA. E-mail: mailto:Claudio.Soto@uth.tmc.edu


5Current address: Laboratorio de Señalización Celular, Centro de Envejecimiento y Regeneración. P. Universidad Catolica de Chile, Santiago, Chile.

Received 8 March 2011; Revised 15 August 2011; Accepted 25 August 2011; Published online 4 October 2011.

Abstract




Alzheimer's disease (AD), the most common type of senile dementia, is associated to the build-up of misfolded amyloid-β (Aβ) in the brain. Although compelling evidences indicate that the misfolding and oligomerization of Aβ is the triggering event in AD, the mechanisms responsible for the initiation of Aβ accumulation are unknown. In this study, we show that Aβ deposition can be induced by injection of AD brain extracts into animals, which, without exposure to this material, will never develop these alterations. The accumulation of Aβ deposits increased progressively with the time after inoculation, and the Aβ lesions were observed in brain areas far from the injection site. Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention.


snip...


Discussion




Recent studies have proposed that other proteinmisfolding disorders besides prion diseases could be transmissible in vivo, following the principles posited by the heretical prion mechanism.8,16–20 If this hypothesis proves to be correct, it will open a novel view on the biology of misfolded protein aggregates and the origin of protein-misfolding disorders, which will have broad-ranging implications for understanding the disease mechanisms and development of new strategies for disease prevention and intervention. In this scenario, our results demonstrate that the administration of brain homogenates containing Ab aggregates can induce some of the neuropathological characteristics of AD in animals, which, without inoculation, will not develop these alterations during their natural lifespan. This experimental paradigm mimic, at least with respect to Ab aggregation, a situation in which a normal person will live his entire life without developing AD abnormalities, unless the process is induced by exposure to material containing seeds of preformed Ab aggregates.



Our findings suggest that in an experimental setting, misfolded Ab aggregates can behave in a similar way as infectious prions. Indeed, as in prion diseases, our data shows that the quantity and degree of maturation of the protein deposits increases with age and that the seeding activity can spread to areas other than the site of injection...



snip... see here ;

Keywords:


amyloid; prion; protein misfolding; disease transmission



POLITICAL BSe and CJD and THE WOW FACTOR $$$



Monday, September 26, 2011


Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

Sunday, September 25, 2011

 

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/mad-cow-scaremongers.html



TSS



CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

Dr McGovern 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 p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative 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://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.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


1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognized 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 emphasizes 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


BSE101/1 0137


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.


JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832


121/YdeStss


92/11.4/1.2




http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf

thought some of you might be interested in this. the thing that concerns me the most is the potential here for iatrogenic transmission of Alzheimer's disease. if true, it would explain a lot...



Friday, August 13, 2010



Creutzfeldt-Jakob disease (CJD) biannual update 13 August 2010 UK Iatrogenic CJD Incidents Report



http://creutzfeldt-jakob-disease.blogspot.com/2010/08/creutzfeldt-jakob-disease-cjd-biannual.html




Tuesday, March 29, 2011



TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE



http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html




Wednesday, September 21, 2011




PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)



http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/prionet-canada-researchers-in-vancouver.html





PP1:



Does A “Prion-Like” Mechanism Contribute to the Spreading of Neuropathology in Parkinson’s Disease?



Patrik Brundin Neuronal Survival Unit; Wallenberg Neuroscience Center; Dept of Experimental Medical Science; Lund University; Lund, Sweden



Key words: Parkinson’s disease, prion mechanism, alpha-synuclein



Neuropathological aggregates of alpha-synuclein in neuronal cytoplasm and neurites are typical features of Parkinson’s disease (PD). These Lewy neurites and Lewy bodies are prominent in substantia nigra, where dopaminergic neurons degenerate. With advancing disease they are also found in several other widespread brain areas, and it has been suggested that they appear in anterior olfactory structures and the dorsal motor nucleus of the vagal nerve even before the substantia nigra is affected. Recent studies demonstrated that Lewy bodies and neurites appear in grafted embryonic neurons.1-3 They stain for Thioflavin S, are immunoreactive for alpha-synuclein phosphorylated at serine residue 129 and exhibit a fibrillar structure in the electron microscope.4 From 2 to 5% (frequency increases over time) of the grafted dopaminergic neurons display Lewy bodies, starting around one decade after surgery. Despite these changes, some of the PD grafted patients still exhibit signs of functional recovery beyond a decade after surgery. We, and others, are currently exploring possible mechanisms underlying the transfer of alpha-synuclein between cells and their relevance to how neuropathology normally spreads in the PD brain.5,6 We have observed that alpha-synuclein indeed can transfer between cells in culture. The process is clearly time-dependent and once inside the new cell the imported alpha-synuclein can seed aggregation of endogenous alpha-synuclein. Furthermore, we have observed transfer of host-derived alpha-synuclein into embryonic dopamine neurons grafted into the striatum of transgenic mice expressing human alpha-synuclein. We propose that a “prion-like” disease mechanism might contribute to the pathogenesis of PD and other chronic neurodegenerative disorders.6



References



1. Li, et al. Nat Med 2008; 14:501-3. 2. Kordower, et al. Nat Med 2008; 14:504-6. 3. Kordower, et al. Mov Disord 2008; 23:2303-6. 4. Li, et al. Mov Disord 2010; [Epub ahead of print]. 5. Brundin, et al. Nat Rev Neurosci 2008; 9:741-5. 6. Brundin, et al. Nat Rev Mol Cell Biol 2010; 11:301-7. PP: Plenary Lectures Previously published online: www.landesbioscience.com/journals/prion/article/12765



DOI: 10.4161/pri.4.3.12765



===========================



WP8-4: Prion-like Induction of Alzheimer-type Proteopathy in Transgenic Mice



Lary C. Walker



Yerkes Center; Emory University; Atlanta, GA USA



Key words: abeta, Alzheimer, amyloid, prion, seeding, strains, transgenic, transmission



Alzheimer’s disease and prion disease both involve the accumulation of disease-specific proteins in the brain, suggesting pathogenic commonalities. In Alzheimer’s disease, the aggregation of the protein fragment Aßis a seminal event. Similar to the templated corruption of prion protein, cerebral Aßdeposition can be induced in ß-amyloid precursor protein (APP)-transgenic mice and rats by the intracerebral injection of Aß-rich brain extracts from patients with Alzheimer’s disease or APP-transgenic mice. Our studies indicate that the characteristics of the seeded deposits depend on the source of the seeding extract, the type of host, and the seeded brain region. We are using the amyloid-binding agent Pittsburgh Compound B (PIB) as a marker of a potential AD-specific form of multimeric Aß, and are attempting to induce alternative conformations in the transgenic mouse Aß-seeding model. In addition, we are investigating non-intracerebral routes of administration and the ability of heterologous agents to induce Aßdeposition. Analysis of Aß-seeding in vivo could yield fresh insights into the origins of idiopathic Alzheimer’s disease.



Acknowledgements



Key collaborators on these studies are Mathias Jucker (U. Tübingen), Rebecca Rosen (Emory U.) and Harry LeVine III (U. Kentucky). Supported by NIH RR-00165 and the CART Foundation.



===========================



PPo9-1: Prion-like Propagation of SOD1 Misfolding in Amyotrophic Lateral Sclerosis



Neil R. Cashman



University of British Columbia; Vancouver, British Columbia Canada



Key words: protein misfolding, mechanisms of neurodegeneration, transmission



Prion-like propagation of protein misfolding has been implicated in Alzheimer’s, Parkinson’s and Huntington’s diseases, and the tauopathies. Amyotrophic lateral sclerosis (ALS) is a common and incurable adult motor neuron disease, in which mutation of the free-radical defense enzyme superoxide dismutase 1 (SOD1) is responsible for a subtype of familial ALS (fALS). We demonstrate that transfection of fALS SOD1 mutants G127X and G85R, as well as overexpression of non-mutant wild-type (wt) SOD1, can induce misfolding of natively-structured wild-type SOD1 in human mesenchymal and neural cell lines, as determined by molecular surface immunoreactivity with misfolding-specific monoclonal antibodies (mAbs), acquisition of protease sensitivity (suggesting structural loosening), generation of reactive oxygen species (ROS) and formation of non-native intermolecular disulfide bonds. Serial transmission of SOD1 misfolding was established by incubation in conditioned media from mtSOD1- or wtSOD1-transfected HEK cells, and knockdown of endogenous SOD1 expression in HEK cells by siRNA abrogated the transmission of SOD1 misfolding, consistent with endogenously expressed SOD1 being the substrate for conformational conversion. Pre-incubation of SOD1-transfected conditioned media with poly-specific SOD1 antibodies or misfolding-specific mAbs also blocked intercellular transducing activity, and passive administration of misfolding-specific mAbs extends survival in the G37R transgenic mouse model of ALS. We conclude that misfolded SOD1 participates in a template-directed misfolding cascade which provides a plausable molecular mechanism for progression of familial and sporadic ALS. Antibody-mediated neutralization of SOD1 misfolding propagation could prove beneficial in human ALS.



================



http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf





Alimentary prion infections: Touch-down in the intestine



Volume 5, Issue 1 January/February/March 2011 Bianca Da Costa Dias, Katarina Jovanovic and Stefan F.T. Weiss View affiliations Hide affiliations Bianca Da Costa DiasSchool of Molecular and Cell Biology; University of the Witwatersrand; Johannesburg, Republic of South Africa Katarina JovanovicSchool of Molecular and Cell Biology; University of the Witwatersrand; Johannesburg, Republic of South Africa Stefan F.T. WeissCorresponding author: stefan.weiss@wits.ac.za School of Molecular and Cell Biology; University of the Witwatersrand; Johannesburg, Republic of South Africa



Neurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of ß-sheets, which accumulate in the Central Nervous System. These diseases, including Morbus Alzheimer, Parkinson disease and Transmissible Spongiform Encephalopathies (TSEs) also termed prion disorders, afflict a substantial proportion of the human population and as such the etiology and pathogenesis of these diseases has been the focus of mounting research. Although many of these diseases arise from genetic mutations or are sporadic in nature, the possible horizontal transmissibility of neurodegenerative diseases poses a great threat to population health. In this article we discuss recent studies which suggest that the “non-transmissible” status bestowed upon Alzheimer and Parkinson diseases may need to be revised as these diseases have been successfully induced through tissue transplants. Furthermore, we highlight the importance of investigating the “natural” mechanism of prion transmission including peroral and perenteral transmission, proposed routes of gastrointestinal uptake and neuroinvasion of ingested infectious prion proteins. We examine the multitude of factors which may influence oral transmissibility and discuss the zoonotic threats which Chronic Wasting Disease (CWD), Bovine Spongiform Encephalopathy (BSE) and Scrapie may pose resulting in vCJD or related disorders. In addition, we suggest that the 37 kDa/67 kDa laminin receptor on the cell surface of enterocytes, a major cell population in the intestine, may play an important role in the intestinal pathophysiology of alimentary prion infections.



http://www.landesbioscience.com/journals/prion/article/14283




Commentary ß-amyloid oligomers and prion protein: Fatal attraction?



Volume 5, Issue 1 January/February/March 2011 Gianluigi Forloni and Claudia Balducci



Gianluigi Forloni Corresponding author: forloni@marionegri.it



Claudia Balducci Biology of Neurodegenerative Diseases Lab; Department of Neuroscience; “Mario Negri” Institute for Pharmacological Research; Milano, Italy



The relationship between Alzheimer disease (AD) and prion-related encephalopathies (TSE) has been proposed by different points of view. Recently, the scientific attention has been attracted by the results proposing the possibility that PrPc, the protein whose pathologic form is responsible of TSE, can mediated the toxic effect of ß amyloid (Aß) oligomers. The oligomers are considered the culprit of the neurodegenerative process associated to AD, although the pathogenic mechanism activated by these small aggregates remain to be elucidated. In the initial study based on the binding screening PrPc was identified as ligand /receptor of Aß oligomers, while long term potentiation (LTP) analysis in vitro and behavioural studies in vivo, demonstrated that the absence of PrPc abolished the damage induced by Aß oligomers. The high affinity binding Aß oligomers-PrPc has been confirmed, whereas a functional role of this association has been excluded by three different studies. We approached this issue by the direct application of Aß oligomers in the brain followed by the behavioural examination of memory deficits. Our data using PrP knock-out mice suggest that Aß 1-42 oligomers are responsible for cognitive impairment in AD but PrPc is not required for their effect. Similarly, in two other studies the LTP alterations induced by Aß 1-42 oligomers was not influenced by the absence of PrP. Possible explanations of these contradictory results are discussed.



http://www.landesbioscience.com/journals/prion/article/14367/





http://www.landesbioscience.com/journals/prion/toc/volume/5/issue/1/




Friday, October 22, 2010



Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis



http://betaamyloidcjd.blogspot.com/2010/10/peripherally-applied-containing.html




Friday, September 3, 2010



Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE



http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html





Wednesday, January 5, 2011



ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions



David W. Colby1,* and Stanley B. Prusiner1,2



http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html



SEE MUCH MORE HERE ;



http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html





http://betaamyloidcjd.blogspot.com/





Wednesday, March 31, 2010



Atypical BSE in Cattle



To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE.



When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.



This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.



http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2





Thursday, August 12, 2010



Seven main threats for the future linked to prions



First threat



The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.



***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.



Second threat



snip...



http://www.neuroprion.org/en/np-neuroprion.html





http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html




http://prionpathy.blogspot.com/





Rural and Regional Affairs and Transport References Committee



The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010



2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49



2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50



http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf




14th ICID International Scientific Exchange Brochure -



Final Abstract Number: ISE.114



Session: International Scientific Exchange



Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009



T. Singeltary



Bacliff, TX, USA



Background:



An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.



Methods:



12 years independent research of available data



Results:



I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.



Conclusion:



I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.



http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf





Monday, May 23, 2011



Atypical Prion Diseases in Humans and Animals 2011



Top Curr Chem (2011)



DOI: 10.1007/128_2011_161



# Springer-Verlag Berlin Heidelberg 2011



Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar



Abstract



Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrPSc), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans.



M.A. Tranulis (*)



Norwegian School of Veterinary Science, Oslo, Norway



e-mail: Michael.Tranulis@nvh.no



S.L. Benestad



Norwegian Veterinary Institute, Oslo, Norway



T. Baron



Agence Nationale de Se´curite´ Sanitaire, ANSES, Lyon, France



H. Kretzschmar



Ludwig-Maximilians University of Munich, Munich, Germany



Keywords Animal Atypical Atypical/Nor98 scrapie BSE-H BSE-L Human Prion disease Prion strain Prion type



http://resources.metapress.com/pdf-preview.axd?code=f433r34h34ugg617&size=largest




snip...SEE MORE HERE ;



http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html






Saturday, June 25, 2011



Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque



"BSE-L in North America may have existed for decades"



http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html





Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.



snip...



The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...



http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf





Thursday, August 4, 2011



Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011
(SEE VIDEO)



http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html







Monday, September 26, 2011



Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011



http://prionopathy.blogspot.com/2011/09/variably-protease-sensitive-prionopathy.html






kindest regards, terry



LAYPERSON




 



 
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Wednesday, June 29, 2011

Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion

Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion


Rodrigo Morales,1,† Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Claudio Soto1

1University of Texas Health Science Center at Houston; Houston, TX USA; 2Universidad de Los Andes; Santiago, Chile; 3Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Rodrigo.MoralesLoyola@uth.tmc.edu


Alzheimer disease (AD) is the most common type of senile dementia. Disease manifestation is characterized by progressive impairment of memory and cognition which is triggered by synaptic dysfunction and neuronal loss. Compelling evidence suggests that misfolding and aggregation of Ab is a hallmark event in the disease pathogenesis. An important unanswered question related to AD involves its etiology since over 90% of the AD cases arise sporadically. Interestingly, misfolding and aggregation of proteins is the main feature of other diseases -termed Protein Misfolding Disorders (PMDs)] which include Transmissible Spongiform Encephalopathies (TSEs), among others. Convincing experimental evidences have shown that the only component of the infectious agent in TSEs is the misfolded form of the prion protein. Strikingly, the molecular mechanisms responsible for prion replication are very similar to the process of amyloid formation in all PMDs, suggesting that all these diseases have the inherent capability of being transmissible. Recent reports have shown that intra-cerebral and intra-peritoneal administration of brain homogenates containing Ab aggregates can accelerate the generation of senile plaques in mice models of AD. However, it remains to be demonstrated if this phenomenon can occur by more relevant routes of administration. The aim of this study was to assess whether AD pathogenesis can be induced intravenously, mimicking the know transmission of prion diseases through blood transfusion. For this purpose we used young tg2576 mice which were injected with blood obtained from 12 months old tg2576 mice (AD-blood) that contains a substantial quantity of cerebral Ab deposits. Mice were sacrificed at 250 days old, a time in which these animals scarcely develop Ab deposits. Interestingly, we observed that infusion of AD-blood induces substantial Ab accumulation in animals that without treatment or injected with wild type blood would barely have any detectable Ab lesion. Plaque deposition was mainly present in cortex and hippocampus, being more abundant in the former. In addition, we observed a decrease in memory in mice challenged with AD-blood. Other features such as brain inflammation and synaptic integrity were also measured. Importantly, similar results were obtained in a second and independent experiment performed in a double transgenic mouse model that develops AD plaques as early as 4 months old. Our results indicate that an AD-like pathogenesis can be induced by intravenous administration of AD-blood, presumably through induction of protein misfolding in a similar way as prion diseases. These findings may open a new avenue to understand the origin of sporadic AD and may provide new strategies for disease intervention and prevention.


http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf



Wednesday, June 29, 2011

TSEAC Meeting August 1, 2011 donor deferral

http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html




TSS
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Wednesday, June 8, 2011

Drugs being developed to tackle CJD could also help prevent Alzheimer’s

Wednesday, June 8, 2011




Drugs being developed to tackle CJD could also help prevent Alzheimer’s



http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/drugs-being-developed-to-tackle-cjd.html
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