Saturday, December 6, 2014

Detection of protein aggregates in brain and cerebrospinal fluid derived from multiple sclerosis patients

Detection of protein aggregates in brain and cerebrospinal fluid derived from multiple sclerosis patients
 
Hypothesis & Theory ARTICLE Front. Neurol., 02 December 2014 | doi: 10.3389/fneur.2014.00251
 
Detection of protein aggregates in brain and cerebrospinal fluid derived from multiple sclerosis patients
 
imageMonique Antoinette David1,2 and imageMourad Tayebi1,3* 1Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX, USA 2Antibody Discovery Laboratory, PrioCam, Houston, TX, USA 3Department of Pathology and Infectious Diseases, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
 
Studies of the properties of soluble oligomer species of amyloidogenic proteins, derived from different proteins with little sequence homology, have indicated that they share a common structure and may share similar pathogenic mechanisms. Amyloid β, tau protein, as well as amyloid precursor protein normally associated with Alzheimer’s disease and Parkinson’s disease were found in lesions and plaques of multiple sclerosis patients. The objective of the study is to investigate whether brain and cerebrospinal fluid (CSF) samples derived from multiple sclerosis patients demonstrate the presence of soluble oligomers normally associated with protein-misfolding diseases such as Alzheimer’s disease. We have used anti-oligomer monoclonal antibodies to immunodetect soluble oligomers in CSF and brain tissues derived from multiple sclerosis patients. In this report, we describe the presence of soluble oligomers in the brain tissue and cerebral spinal fluid of multiple sclerosis patients detected with our monoclonal anti-oligomer antibodies with Western blot and Sandwich enzyme-linked immunosorbent assay (sELISA). These results might suggest that protein aggregation plays a role in multiple sclerosis pathogenesis although further and more refined studies are needed to confirm the role of soluble aggregates in multiple sclerosis.
 
Finally, co-morbidities are a recognized feature following autopsy of patients with PMDs; for instance, both Parkinson’s and AD have been recognized in same patients. We therefore wanted to assess whether brain homogenates derived from MS patients displayed PK-resistant prions (Figure 4B) and we also checked for the presence of Aβ and α-synuclein (data not shown). Brain homogenates from patients with MS (Secondary progressive) did not display any presence of PK-resistant prions as assessed by anti-prion antibody and also failed to demonstrate binding for Aβ and α-synuclein.
 
Our study shows for the time that protein aggregates detected by anti-oligomer specific antibodies are associated with MS. The data generated so far does not allow to reach a substantive conclusion in relation to the involvement of these proteins aggregates in MS pathogenesis. Protein aggregation associated with MS has been described previously in a rodent model of MS (16). Dasgupta and colleagues have demonstrated increased protein aggregation in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). In their study, they argue that accumulation of misfolded proteins is caused by increased rate of protein oxidation and reduced proteasome degradation, both seen in MS (17) and EAE (18, 19).
 
In conclusion, for the first time, we demonstrate the presence of soluble oligomers, normally associated with PMDs, in MS tissues and CSF. Although the pathogenic relevance of these MS associated soluble oligomers to disease process remains to be investigated, this study sets the ground for further investigating this relationship. This study proposes a novel alternative in understanding the pathogenesis of MS.
 
 
 
 
Physiol Rev. 2009 Oct;89(4):1105-52. doi: 10.1152/physrev.00006.2009.
 
Prions: protein aggregation and infectious diseases.
 
Aguzzi A1, Calella AM. Author information 1Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland. adriano.aguzzi@usz.ch
 
Abstract
 
Transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative diseases that affect humans and a large variety of animals. The infectious agent responsible for TSEs is the prion, an abnormally folded and aggregated protein that propagates itself by imposing its conformation onto the cellular prion protein (PrPC) of the host. PrPC is necessary for prion replication and for prion-induced neurodegeneration, yet the proximal causes of neuronal injury and death are still poorly understood. Prion toxicity may arise from the interference with the normal function of PrPC, and therefore, understanding the physiological role of PrPC may help to clarify the mechanism underlying prion diseases. Here we discuss the evolution of the prion concept and how prion-like mechanisms may apply to other protein aggregation diseases. We describe the clinical and the pathological features of the prion diseases in human and animals, the events occurring during neuroinvasion, and the possible scenarios underlying brain damage. Finally, we discuss potential antiprion therapies and current developments in the realm of prion diagnostics.
 
snip...
 
Another major unresolved issue is the extent to which the induced amyloidotic lesions can spread from localized sites of seeding by the inoculum to other sites within the host. Surprisingly, a recent study reported that healthy fetal tissue grafted into the brains of Parkinson’s disease patients acquired cytoplasmic -synuclein-rich Lewy bodies, suggesting that misfolded -synuclein spreads to healthy cells and acts as a template for the conversion of native -helices to pathogenic -sheets (299).
 
Type 2 diabetes is yet another disease whose pathogenesis may involve ordered protein aggregation. Evidence for this was discovered early on (373) but was largely forgotten for almost a century. It is now evident that aggregation of islet amyloid polypeptide (IAPP) is an exceedingly frequent feature of type 2 diabetes. IAPP amyloid damages the insulin-producing -cells within pancreatic islets and may crucially contribute to the pathogenesis of diabetes (233). It is unknown, however, whether IAPP deposition simply accrues linearly with IAPP production, or whether it spreads in a prion-like fashion from one pancreatic islet to the next.
 
In summary, the role of protein misfolding and aggregation in various human diseases has been clearly established in the past decade, yet an important challenge for the coming years will be to determine whether the prion mechanism of disease transmission might be operating in other human diseases, some of which are highly prevalent.
 
snip...
 
 
Immune responses in rapidly progressive dementia: a comparative study of neuroinflammatory markers in Creutzfeldt-Jakob disease, Alzheimer’s disease and multiple sclerosis
 
Katharina Stoeck†, Matthias Schmitz*†, Elisabeth Ebert, Christian Schmidt and Inga Zerr
 
Abstract
 
Immunological responses may contribute to disease progression and clinical heterogeneity in neurodegenerative dementia, for example, Alzheimer’s disease (AD) and Creutzfeldt-Jakob disease (CJD). Recently, a rapidly progressive form of AD (rpAD) has been described. On neuropathological grounds classical AD and rpAD are not distinguishable at present. All those protein aggregopathies show a state of chronic inflammation with microglia activation and production of proinflammatory cytokines. In this context, it is hypothesized that the severity of the surrounding inflammation substantially contributes to disease progression and accelerated disease courses as seen in rpAD. Using a cytokine multiplex array based on Luminex Technology, we studied 17 pro- and anti-inflammatory cytokines in cerebrospinal fluid (CSF) and serum from patients with classical dementia (AD) or rapidly progressive dementia (Creutzfeldt-Jakob disease (CJD), rpAD). For controls, we chose patients with multiple sclerosis (MS) and non-neurodegenerative diseases. We found a significant and isolated elevation of proinflammatory cytokines (IL-13, TNF-α and G-CSF) in the serum of rpAD patients. In CSF, IL-8 and MCP-1 chemokines were significantly elevated in CJD patients and MCP-1 in AD patients. In conclusion, we found a characteristic proinflammatory cytokine response in the serum of rpAD patients. It might explain the more rapidly progressive course of the rpAD subform and can be helpful in distinguishing between classical AD and rpAD.
 
Abbreviations Aβ: amyloid beta; AD: Alzheimer’s disease; CJD: Creutzfeldt-Jakob disease; CSF: cerebrospinal fluid; MS: multiple sclerosis; PrP: prion protein; rpAD: a rapidly progressive form of Alzheimer’s disease.
 
 
Wednesday, November 13, 2013
 
Spontaneous Generation of Infectious Prion Disease in Transgenic Mice
 
***These considerations enable us to hypothesize that the BSE epidemic could have begun by a random genetic mutation that was able to generate de novo infectious prions, which were included in meat and bone meal fed to cattle and then broadly expanded in the cattle population. According to this hypothesis, a key strategy for controlling BSE would involve preventing cows from consuming products from cows with spontaneous cases of BSE.***
 
 
Tuesday, May 7, 2013
 
Proteinopathies, a core concept for understanding and ultimately treating degenerative disorders?
 
 
Sunday, February 10, 2013
 
Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?
 
 
Wednesday, May 16, 2012
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
Proposal ID: 29403
 
 
Wednesday, September 21, 2011
 
PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)
 
 
Friday, September 3, 2010
 
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
 
 
 
 
 
 
 
 
 
 
 
 
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease
 
Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014
 
 
Singeltary comment ;
 
 
Sunday, November 23, 2014
 
Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European
 
‘’The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.’’
 
 
Friday, December 5, 2014
 
SPECIAL ALERT The OIE recommends strengthening animal disease surveillance worldwide
 
OIE BSE TSE PRION AKA MAD COW DISEASE ?
 
‘’the silence was deafening’’ ...tss
 
 
TSS

Saturday, October 11, 2014

UC Berkeley, UCSF researchers team up to create center for neurodegenerative disease research

UC Berkeley, UCSF researchers team up to create center for neurodegenerative disease research

 

Published on October 10, 2014 at 1:17 AM

 

Investigators will explore role of decline in protein quality-control in dementias, other illnesses

 

Researchers at UC San Francisco and UC Berkeley have teamed up to create an innovative, integrated center for research on neurodegenerative diseases. Supported by a $3 million grant from the Glenn Foundation for Medical Research, the new center aims to pave the way to developing novel treatments for diseases such as Alzheimer's disease and Parkinson's disease by investigating the many ways that proteins can malfunction within cells.

 

In particular, the center's work will focus on a type of protein called the prion, which displays characteristics of infectious agents and is responsible for "mad cow" disease and a related, devastating human brain disorder known as Creutzfeldt-Jakob disease (CJD).

 

Stanley B. Prusiner, MD, UCSF professor of neurology, and Andrew Dillin, PhD, the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research at UCB and a Howard Hughes Medical Institute investigator, will codirect the new inter-campus program, known as the Paul F. Glenn Center for Aging Research. Ten additional researchers from UCSF and 13 from UCB will contribute to the center's work, with more recruitments to come.

 

"The Glenn Foundation is pleased to welcome UCSF and UC Berkeley to the Glenn Consortium for Research in Aging," said Mark R. Collins, president of the Glenn Foundation for Medical Research, which is based in Santa Barbara, Calif. "I had the pleasure to work with Dr. Dillin previously, when he led the Glenn Center for Aging Research at the Salk Institute for Biological Sciences prior to moving to UC Berkeley. I've known Dr. Prusiner and followed his work for many years and it is a propitious time for us to assist these two leaders in biological research to discover treatments for age-related neurodegenerative disease."

 

In 1997, Prusiner, director of UCSF's Institute for Neurodegenerative Diseases, received the Nobel Prize in Physiology or Medicine for his discovery of prions, which he demonstrated were an abnormally folded form of normal proteins that set up a template for replication in the brain. According to Prusiner, recent work provides persuasive evidence that, in addition to mad cow disease and CJD, many common neurodegenerative diseases, including Alzheimer's and Parkinson's, are caused by abnormally folded forms of normal proteins functioning as prions.

 

Dillin agrees that prions are ideal targets for research and novel therapeutic approaches. "The Glenn Foundation's confidence to support our hypothesis is greatly appreciated," he said, adding that the combination of UCSF's medical mission with the strong basic research traditions of both campuses will make the new Glenn Center's work uniquely powerful.

 

Proteins are crucial for many of a cell's normal functions, but as people age, cells' quality-control mechanisms become less efficient. Normally these systems ensure that proteins are properly formed, and target badly formed or "worn-out" proteins for destruction. But as the effectiveness of cellular quality control wanes over time, improperly formed proteins, including prions, can begin to accumulate.

 

Badly formed proteins, called "misfolded" by biologists, cannot carry out their required functions and, even worse, they can stick to one another and to other cellular components, sometimes leading to devastating physiological consequences. Prions are particularly problematic because they can act like a template, converting properly formed proteins into additional prions, essentially spreading protein misfolding like an infection.

 

Seeking ways to counteract the accumulation of misfolded proteins, the new Glenn Center's researchers will investigate the many cellular quality-control mechanisms that act throughout a protein's lifetime, from when proteins are first made, to the interactions that help them reach their proper functional state, to the transport processes that take them to their final destinations, to their ultimate degradation when they can no longer serve their purpose.

 

Together, the UCSF and UCB researchers affiliated with the center have complementary expertise in all of these areas, and the center's ultimate goal is to develop new anti-prion drugs, Dillin said. "At Berkeley, we aim to build the basic scientific knowledge to leverage clinical and therapeutic discoveries at UCSF."

 

According to Prusiner, "the newest research indicates that Alzheimer's alone kills as many people every year as cancer does, but it only receives one-tenth of the funding that we dedicate to cancer research. We are grateful to The Glenn Foundation for their support in the battle against neurodegenerative diseases."

 

Source:

 

University of California - San Francisco

 


 

Wednesday, May 16, 2012

 

Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?

 

Proposal ID: 29403

 


 

Wednesday, September 21, 2011

 

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

 


 

 Wednesday, January 5, 2011

 

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

 

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

 


 


 

Friday, September 3, 2010

 

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

 


 

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. 93/01.05/4.1

 


 

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/YdeS 92/11.4/1.2

 


 

BSE101/1 0136

 

IN CONFIDENCE

 

CMO

 

From: Dr J S Metters DCMO

 

4 November 1992

 

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

 


 

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

 


 

Tuesday, July 1, 2014

 

Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice

 


 

Tuesday, November 26, 2013

 

Transmission of multiple system atrophy prions to transgenic mice

 


 

Tuesday, December 17, 2013

 

Alzheimer's Disease U.K. diagnosed by region in each of the last five years [179852]

 


 

Sunday, September 7, 2014

 

Twice as many cases of early dementia than was thought Alzheimer’s Society, the London School of Economics and the Institute of Psychiatry

 


 


 

Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014

 

Transmissible Spongiform Encephalopathy TSE Prion Disease have now been discovered in a wide verity of species across North America. typical C-BSE, atypical L-type BASE BSE, atypical H-type BSE, atypical H-G BSE, of the bovine, typical and atypical Scrapie strains, in sheep and goats, with atypical Nor-98 Scrapie spreading coast to coast in about 5 years. Chronic Wasting Disease CWD in cervid is slowly spreading without any stopping it in Canada and the USA and now has mutated into many different strains. Transmissible Mink Encephalopathy TME outbreaks. These Transmissible Spongiform Encephalopathy TSE Prion Disease have been silently mutating and spreading in different species in North America for decades.

 

The USDA, FDA, et al have assured us of a robust Triple BSE TSE prion Firewall, of which we now know without a doubt, that it was nothing but ink on paper. Since the 1997 mad cow feed ban in the USA, literally tons and tons of banned mad cow feed has been put out into commerce, never to return, as late as December of 2013, serious, serious breaches in the FDA mad cow feed ban have been documented. The 2004 enhanced BSE surveillance program was so flawed, that one of the top TSE prion Scientist for the CDC, Dr. Paul Brown stated ; Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive. see ; http://www.upi.com/Health_News/2006/03/15/Analysis-What-that-mad-cow-means/UPI-12841142465253/

 

The BSE surveillance and testing have also been proven to be flawed, and the GAO and OIG have both raised serious question as to just how flawed it has been (see GAO and OIG reports). North America has more documented TSE prion disease, in different documented species (excluding the Zoo BSE animals in the EU), then any other place on the Globe. This does not include the very likelihood that TSE prion disease in the domestic feline and canine have been exposed to high doses of the TSE prion disease vid pet food. To date, it’s still legal to include deer from cwd zone into pet food or deer food. Specified Risk Material i.e. SRM bans still being breach, as recently as just last month.

 

nvCJD or what they now call vCJD, another case documented in Texas last month, with very little information being released to the public on about this case? with still the same line of thought from federal officials, ‘it can’t happen here’, so another vCJD blamed on travel of a foreign animal disease from another country, while ignoring all the BSE TSE Prion risk factors we have here in the USA and Canada, and the time that this victim and others, do spend in the USA, and exposed to these risk factors, apparently do not count in any way with regard to risk factor. a flawed process of risk assessment.

 

sporadic CJD, along with new TSE prion disease in humans, of which the young are dying, of which long duration of illness from onset of symptoms to death have been documented, only to have a new name added to the pot of prion disease i.e. sporadic GSS, sporadic FFI, and or VPSPR. I only ponder how a familial type disease could be sporadic with no genetic link to any family member? when the USA is the only documented Country in the world to have documented two different cases of atypical H-type BSE, with one case being called atypical H-G BSE with the G meaning Genetic, with new science now showing that indeed atypical H-type BSE is very possible transmitted to cattle via oral transmission (Prion2014). sporadic CJD and VPSPR have been rising in Canada, USA, and the UK, with the same old excuse, better surveillance. You can only use that excuse for so many years, for so many decades, until one must conclude that CJD TSE prion cases are rising. a 48% incease in CJD in Canada is not just a blip or a reason of better surveillance, it is a mathematical rise in numbers. More and more we are seeing more humans exposed in various circumstance in the Hospital, Medical, Surgical arenas to the TSE Prion disease, and at the same time in North America, more and more humans are becoming exposed to the TSE prion disease via consumption of the TSE prion via deer and elk, cattle, sheep and goats, and for those that are exposed via or consumption, go on to further expose many others via the iatrogenic modes of transmission of the TSE prion disease i.e. friendly fire. I pondered this mode of transmission via the victims of sporadic FFI, sporadic GSS, could this be a iatrogenic event from someone sub-clinical with sFFI or sGSS ? what if?

 

Two decades have passed since Dr. Ironside first confirmed his first ten nvCJD victims in 1995. Ten years later, 2005, we had Dr. Gambetti and his first ten i.e. VPSPR in younger victims. now we know that indeed VPSPR is transmissible. yet all these TSE prion disease and victims in the USA and Canada are being pawned off as a spontaneous event, yet science has shown, the spontaneous theory has never been proven in any natural case of TSE prion disease, and scientist have warned, that they have now linked some sporadic CJD cases to atypical BSE, to atypical Scrapie, and to CWD, yet we don’t here about this in the public domain. We must make all human and animal TSE prion disease reportable in every age group, in ever state and internationally, we must have a serious re-evaluation and testing of the USA cattle herds, and we must ban interstate movement of all cervids. Any voluntary effort to do any of this will fail. Folks, we have let the industry run science far too long with regards to the TSE prion disease. While the industry and their lobbyist continues to funnel junk science to our decision policy makers, Rome burns. ...end

 

REFERENCES

 

[all scientific peer review studies and other scientific information I have put into blogs, to shorten reference data. I DO NOT advertise or make money from this, this information is for education use...lost my mom to the hvCJD, and just made a promise, never forget, and never let them forget. ...TSS]

 

Sunday, June 29, 2014

 

Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014

 


 

Saturday, June 14, 2014

 

Rep. Rosa DeLauro (D-CT) Calls for Briefing on Beef Recalled for Mad Cow Potential Rep. Rosa DeLauro (D-CT)

 


 

Thursday, June 12, 2014

 

Missouri Firm Recalls Ribeye and Carcass Products That May Contain Specified Risk Materials 4,012 pounds of fresh beef products because the dorsal root ganglia may not have been completely removed

 


 

Thursday, October 02, 2014

 

[Docket No. APHIS-2013-0064] Concurrence With OIE Risk Designations for Bovine Spongiform Encephalopathy

 


 

 Thursday, July 03, 2014

 

*** How Chronic Wasting Disease is affecting deer population and what’s the risk to humans and pets?

 


 

 Tuesday, July 01, 2014

 

*** CHRONIC WASTING DISEASE CWD TSE PRION DISEASE, GAME FARMS, AND POTENTIAL RISK FACTORS THERE FROM

 


 

Tuesday, October 07, 2014

 

Wisconsin white-tailed deer tested positive for CWD on a Richland County breeding farm, and a case of CWD has been discovered on a Marathon County hunting preserve

 


 

Thursday, October 02, 2014

 

IOWA TEST RESULTS FROM CAPTIVE DEER HERD WITH CHRONIC WASTING DISEASE RELEASED 79.8 percent of the deer tested positive for the disease

 


 

 CWD STRAINS TO HUMANS ???

 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).

 


 

as I said, what if ?

 

*** our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ***

 


 

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

 

Thursday, January 2, 2014

 

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ??? ***

 

WHAT IF ?

 


 

Saturday, April 19, 2014

 

Exploring the zoonotic potential of animal prion diseases: In vivo and in vitro approaches

 


 

*** PPo3-7: Prion Transmission from Cervids to Humans is Strain-dependent

 

*** Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP,

 

*** indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains.

 

PPo2-27:

 

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

 

*** Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.

 

PPo2-7:

 

Biochemical and Biophysical Characterization of Different CWD Isolates

 

*** The data presented here substantiate and expand previous reports on the existence of different CWD strains.

 


 

Envt.07:

 

Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

 

***The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

 


 

>>>CHRONIC WASTING DISEASE , THERE WAS NO ABSOLUTE BARRIER TO CONVERSION OF THE HUMAN PRION PROTEIN<<<

 

*** PRICE OF CWD TSE PRION POKER GOES UP 2014 ***

 

Transmissible Spongiform Encephalopathy TSE PRION update January 2, 2014

 

Wednesday, January 01, 2014

 

Molecular Barriers to Zoonotic Transmission of Prions

 

*** chronic wasting disease, there was no absolute barrier to conversion of the human prion protein.

 

*** Furthermore, the form of human PrPres produced in this in vitro assay when seeded with CWD, resembles that found in the most common human prion disease, namely sCJD of the MM1 subtype.

 


 


 

PRION2013 CONGRESSIONAL ABSTRACTS CWD

 

Sunday, August 25, 2013

 

HD.13: CWD infection in the spleen of humanized transgenic mice

 

***These results indicate that the CWD prion may have the potential to infect human peripheral lymphoid tissues.

 

Oral.15: Molecular barriers to zoonotic prion transmission: Comparison of the ability of sheep, cattle and deer prion disease isolates to convert normal human prion protein to its pathological isoform in a cell-free system ***However, they also show that there is no absolute barrier ro conversion of human prion protein in the case of chronic wasting disease.

 

PRION2013 CONGRESSIONAL ABSTRACTS CWD

 

Sunday, August 25, 2013

 

***Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission

 


 

there is in fact evidence that the potential for cwd transmission to humans can NOT be ruled out.

 

I thought your readers and hunters and those that consume the venison, should have all the scientific facts, personally, I don’t care what you eat, but if it effects me and my family down the road, it should then concern everyone, and the potential of iatrogenic transmission of the TSE prion is real i.e. ‘friendly fire’, medical, surgical, dental, blood, tissue, and or products there from...like deer antler velvet and TSE prions and nutritional supplements there from, all a potential risk factor that should not be ignored or silenced. ...

 

the prion gods at the cdc state that there is ;

 

''no strong evidence''

 

but let's see exactly what the authors of this cwd to human at the cdc state ;

 

now, let’s see what the authors said about this casual link, personal communications years ago. see where it is stated NO STRONG evidence. so, does this mean there IS casual evidence ????

 

“Our conclusion stating that we found no strong evidence of CWD transmission to humans”

 

From: TSS (216-119-163-189.ipset45.wt.net)

 

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

 

Date: September 30, 2002 at 7:06 am PST

 

From: "Belay, Ermias"

 

To:

 

Cc: "Race, Richard (NIH)" ; ; "Belay, Ermias"

 

Sent: Monday, September 30, 2002 9:22 AM

 

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

 

Dear Sir/Madam,

 

In the Archives of Neurology you quoted (the abstract of which was attached to your email), we did not say CWD in humans will present like variant CJD.

 

That assumption would be wrong. I encourage you to read the whole article and call me if you have questions or need more clarification (phone: 404-639-3091). Also, we do not claim that "no-one has ever been infected with prion disease from eating venison." Our conclusion stating that we found no strong evidence of CWD transmission to humans in the article you quoted or in any other forum is limited to the patients we investigated.

 

Ermias Belay, M.D. Centers for Disease Control and Prevention

 

-----Original Message-----

 

From:

 

Sent: Sunday, September 29, 2002 10:15 AM

 

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

 

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

 

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

 

Thursday, April 03, 2008

 

A prion disease of cervids: Chronic wasting disease

 

2008 1: Vet Res. 2008 Apr 3;39(4):41

 

A prion disease of cervids: Chronic wasting disease

 

Sigurdson CJ.

 

snip...

 

*** twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center***,

 

snip...

 

full text ;

 


 


 


 

***********CJD REPORT 1994 increased risk for consumption of veal and venison and lamb***********

 

CREUTZFELDT JAKOB DISEASE SURVEILLANCE IN THE UNITED KINGDOM THIRD ANNUAL REPORT AUGUST 1994

 

Consumption of venison and veal was much less widespread among both cases and controls. For both of these meats there was evidence of a trend with increasing frequency of consumption being associated with increasing risk of CJD. (not nvCJD, but sporadic CJD...tss)

 

These associations were largely unchanged when attention was restricted to pairs with data obtained from relatives. ...

 

Table 9 presents the results of an analysis of these data.

 

There is STRONG evidence of an association between ‘’regular’’ veal eating and risk of CJD (p = .0.01).

 

Individuals reported to eat veal on average at least once a year appear to be at 13 TIMES THE RISK of individuals who have never eaten veal.

 

There is, however, a very wide confidence interval around this estimate. There is no strong evidence that eating veal less than once per year is associated with increased risk of CJD (p = 0.51).

 

The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04).

 

There is some evidence that risk of CJD INCREASES WITH INCREASING FREQUENCY OF LAMB EATING (p = 0.02).

 

The evidence for such an association between beef eating and CJD is weaker (p = 0.14). When only controls for whom a relative was interviewed are included, this evidence becomes a little STRONGER (p = 0.08).

 

snip...

 

It was found that when veal was included in the model with another exposure, the association between veal and CJD remained statistically significant (p = < 0.05 for all exposures), while the other exposures ceased to be statistically significant (p = > 0.05).

 

snip...

 

In conclusion, an analysis of dietary histories revealed statistical associations between various meats/animal products and INCREASED RISK OF CJD. When some account was taken of possible confounding, the association between VEAL EATING AND RISK OF CJD EMERGED AS THE STRONGEST OF THESE ASSOCIATIONS STATISTICALLY. ...

 

snip...

 

In the study in the USA, a range of foodstuffs were associated with an increased risk of CJD, including liver consumption which was associated with an apparent SIX-FOLD INCREASE IN THE RISK OF CJD. By comparing the data from 3 studies in relation to this particular dietary factor, the risk of liver consumption became non-significant with an odds ratio of 1.2 (PERSONAL COMMUNICATION, PROFESSOR A. HOFMAN. ERASMUS UNIVERSITY, ROTTERDAM). (???...TSS)

 

snip...see full report ;

 


 

Thursday, October 10, 2013

 

*************CJD REPORT 1994 increased risk for consumption of veal and venison and lamb**************

 


 

CJD9/10022

 

October 1994

 

Mr R.N. Elmhirst Chairman British Deer Farmers Association Holly Lodge Spencers Lane BerksWell Coventry CV7 7BZ

 

Dear Mr Elmhirst,

 

CREUTZFELDT-JAKOB DISEASE (CJD) SURVEILLANCE UNIT REPORT

 

Thank you for your recent letter concerning the publication of the third annual report from the CJD Surveillance Unit. I am sorry that you are dissatisfied with the way in which this report was published.

 

The Surveillance Unit is a completely independant outside body and the Department of Health is committed to publishing their reports as soon as they become available. In the circumstances it is not the practice to circulate the report for comment since the findings of the report would not be amended. In future we can ensure that the British Deer Farmers Association receives a copy of the report in advance of publication.

 

The Chief Medical Officer has undertaken to keep the public fully informed of the results of any research in respect of CJD. This report was entirely the work of the unit and was produced completely independantly of the the Department.

 

The statistical results reqarding the consumption of venison was put into perspective in the body of the report and was not mentioned at all in the press release. Media attention regarding this report was low key but gave a realistic presentation of the statistical findings of the Unit. This approach to publication was successful in that consumption of venison was highlighted only once by the media ie. in the News at one television proqramme.

 

I believe that a further statement about the report, or indeed statistical links between CJD and consumption of venison, would increase, and quite possibly give damaging credence, to the whole issue. From the low key media reports of which I am aware it seems unlikely that venison consumption will suffer adversely, if at all.

 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

Wednesday, September 17, 2014

 

*** Cost benefit analysis of the development and use of ante-mortem tests for transmissible spongiform encephalopathies ***

 

BOTTOM LINE $$$

 

IF YOU TEST, YOU FIND, and the more you test, the more you will find.

 

HUMANS ARE EXPENDABLE WITH A SLOW, LONG INCUBATING, 100% FATAL DISEASE, ONCE CLINICAL DISEASE...tss

 


 

Monday, June 02, 2014

 

Confirmed Human BSE aka mad cow Variant CJD vCJD or nvCJD Case in Texas

 


 


 


 

 

 

Terry S. Singeltary Sr.

Sunday, September 7, 2014

Twice as many cases of early dementia than was thought Alzheimer’s Society, the London School of Economics and the Institute of Psychiatry

Alzheimer’s Society, the London School of Economics and the Institute of Psychiatry
 
Twice as many cases of early dementia than was thought
 
Charity calls for more help for younger people with dementia as new figures disclose twice as many cases as was thought among those aged between 30 and 65
 
Charity calls for more help for younger people with dementia as new figures disclose thousands of cases among those aged between 30 and 65
 
Surveys have found that dementia is the most feared condition among those aged 55 and over Photo: Alamy
 
Laura Donnelly By Laura Donnelly, Health Editor
 
9:00PM BST 06 Sep 2014
 
More than twice as many people in the UK have dementia before the age of 65 than was previously thought, new figures show.
 
A report due to be published this week says that 42,000 people are now estimated to be suffering early onset dementia, including thousands of cases among those in their 40s, and more than 700 cases among those in their 30s.
 
The new statistics also show the condition is slightly more common among men than women.
 
Experts said doctors too often missed symptoms of dementia in younger people, assuming they were too young to be suffering from the condition. They said services and society needed to do more to help those coming to terms with a diagnosis of dementia.
 
The figures, due to be published tomorrow, come from a state of the nation report by the Alzheimer’s Society, the London School of Economics and the Institute of Psychiatry, which will show the cost of dementia to the NHS and social services.
 
Previous estimates had suggested that just 17,000 cases of dementia involve younger people. But the new figures suggest 42,325 people below the age of 65 are currently suffering from such conditions – representing roughly five per cent of all cases of dementia. Three quarters of cases are among those aged between 60 and 65, but cases can occur among those in their 50s, 40s and even in their 30s.
 
Jeremy Hughes, chief executive at Alzheimer’s Society said: “For too long dementia has been perceived as a natural part of ageing which only affects the oldest of the old in our society.
 
“Say the word Alzheimer’s and many people picture a frail, elderly person in a care home. The risk of developing dementia does increase with age, but the reality is that dementia is caused by diseases of the brain that don’t discriminate. “
 
Surveys have found that dementia is the most feared condition among those aged 55 and over.
 
Mr Hughes said: “Many people will be coming to terms with the symptoms while still in work, perhaps looking after children and paying a mortgage. Too often we hear of people reporting memory loss to their doctor in mid-life, but being misdiagnosed because they are considered too young to have dementia. “
 
He said services need to ensure that younger adults were able to access specialist treatment and support.
 
The new estimates suggest that of the 42,325 cases of early-onset dementia in the UK, 21,519 cases are in men while 20,806 are in women. Around 32,000 of the cases involve those aged 60 to 65, with 7,700 cases among those in their 50s, 2,010 cases among those in their 40s, and 707 cases among those in their 30s, the figures show.
 
While Alzheimer’s disease is the most common form of dementia among the elderly, in those under the age of 65, it represents just one in three cases. In some cases, there is a family history of early-onset Alzheimer’s disease.
 
Among younger people, the second most common cause is vascular dementia, which occurs when there are problems in the blood supply to the brain. One in five cases of dementia in the under 65s are caused by this.
 
Around one in ten cases of dementia in younger people are alcohol-related, and 10 per cent are caused by dementia with Lewy bodies, a build up of tiny protein deposits in the brain .
 
A further 12 per cent are caused by front-temporal dementia, which is a more common cause of dementia among those aged between 45 and 65 than among dementias in older people, and often relates to a family history of the disease. Rarer forms of dementia – linked to conditions such as Parkinson's disease, Huntington’s disease and Creutzfeldt-Jakob disease - also explain a higher proportion of dementias in younger people than they do in the elderly.
 
The report also forecasts that the number of people with early-onset dementia is set to rise by 20 per cent over the next four decades, with more than 50,000 cases expected by 2051.
 
Susan Hulme, from Camarthenshire, South Wales, was diagnosed with Alzheimer’s disease last year, at the age of 59. She said she had been struggling with memory problems for three years, which had been attributed to stress, or sinus problems.
 
When she visited her GP last year, and found herself unable to recall the reason for her visit, she was referred to a memory clinic, who made the diagnosis, and prescribed medication which can slow its impact.
 
Ms Hulme, a former civil servant, said: “In a way it felt like a relief to get the diagnosis, because I knew something was wrong for several years, I had been really struggling with my memory, and with a kind of fuzzy feeling that was worst in the mornings – but it was a real shock that it was Alzheimer’s disease, I thought that was something that only came with old age.”
 
She had already taken voluntary redundancy, after suffering what she had thought was stress.
 
Telling people about her diagnosis was one of the most difficult parts of coming to terms with the condition, she said, calling for more funding of services for younger people, to provide support.
 
“I don’t think most people realise this is something that could happen at this age. Telling my partner and my children was one of the most difficult things to do,” she said.
 
 
 
Saturday, May 25, 2013
 
 Brain homogenates from human tauopathies induce tau inclusions in mouse brain
 
 
 
 
Sunday, February 10, 2013
 
 Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?
 
 
 
 
 
 
Wednesday, May 16, 2012
 
 Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
Background
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
 
Methods
 
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
 
Results
 
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
 
Conclusions
 
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
 
end...tss
 
SEE FULL TEXT AND SOURCE REFERENCES ;
 
Wednesday, May 16, 2012
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
 
 Wednesday, September 21, 2011
 
 PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)
 
 
 
 
Wednesday, January 5, 2011
 
 ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
 
 David W. Colby1,* and Stanley B. Prusiner1,2
 
 
 
 
Friday, September 3, 2010
 
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
 
 
 
 
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. 93/01.05/4.1
 
 
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/YdeS 92/11.4/1.2
 
 
 
BSE101/1 0136
 
IN CONFIDENCE
 
CMO
 
From: Dr J S Metters DCMO
 
4 November 1992
 
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
 
 
 
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
 
 
Tuesday, July 1, 2014
 
Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice
 
 
Tuesday, November 26, 2013
 
Transmission of multiple system atrophy prions to transgenic mice
 
 
Tuesday, December 17, 2013
 
Alzheimer's Disease U.K. diagnosed by region in each of the last five years [179852]
 
 
 
TSS
 

Tuesday, July 1, 2014

Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice

Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice

 
Jan Stöhra,b, Carlo Condelloa, Joel C. Wattsa,b,1, Lillian Blocha, Abby Oehlerc, Mimi Nickd, Stephen J. DeArmonda,c, Kurt Gilesa,b, William F. DeGradod, and Stanley B. Prusinera,b,2 Author Affiliations

 
aInstitute for Neurodegenerative Diseases, Departments of bNeurology and cPathology, and dPharmaceutical Chemistry, University of California, San Francisco, CA 94143 Contributed by Stanley B. Prusiner, May 14, 2014 (sent for review April 15, 2014)

 
Abstract Authors & Info SI Metrics PDF PDF + SI Significance Alzheimer’s disease is the most common neurodegenerative disorder; it is a progressive dementia for which there is currently no effective therapeutic intervention. The brains of patients with Alzheimer’s disease exhibit numerous amyloid β (Aβ) amyloid plaques and tau-laden neurofibrillary tangles. Our studies show that synthetic Aβ peptides can form prions that infect mice and induce Aβ amyloid plaque pathology. Two different Aβ prion strains were produced from Aβ peptides. When injected into transgenic mice, one Aβ strain produced large plaques and the other strain induced small but more numerous plaques. Our findings may help to delineate the molecular pathogenesis of Alzheimer’s disease and the development of anti-Aβ prion therapeutics.

 
Abstract An increasing number of studies continue to show that the amyloid β (Aβ) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of Aβ prions formed from synthetic Aβ peptides composed of either 40 or 42 residues. Modifying the conditions for Aβ polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic Aβ40 and Aβ42 prions produced a sustained rise in the bioluminescence imaging signal in the brains of bigenic Tg(APP23:Gfap-luc) mice, indicative of astrocytic gliosis. Pathological investigations showed that synthetic Aβ40 prions produced amyloid plaques containing both Aβ40 and Aβ42 in the brains of inoculated bigenic mice, whereas synthetic Aβ42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of Aβ42. Synthetic Aβ40 preparations consisted of long straight fibrils; in contrast, the Aβ42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced Aβ42 fibrils that were indistinguishable from Aβ40 fibrils produced in the absence or presence of SDS. Moreover, the Aβ amyloid plaques in the brains of bigenic mice inoculated with Aβ42 prions prepared in the presence of SDS were similar to those found in mice that received Aβ40 prions. From these results, we conclude that the composition of Aβ plaques depends on the conformation of the inoculated Aβ polymers, and thus, these inocula represent distinct synthetic Aβ prion strains.

 
Alzheimer's disease in vitro neurodegenerative diseases Footnotes ↵1Present address: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.

 

↵2To whom correspondence should be addressed. E-mail: stanley@ind.ucsf.edu. Author contributions: J.S., C.C., and S.B.P. designed research; J.S., C.C., J.C.W., L.B., A.O., and M.N. performed research; J.S., C.C., S.J.D., K.G., W.F.D., and S.B.P. analyzed data; and J.S. and S.B.P. wrote the paper.

 

The authors declare no conflict of interest.

 

This article contains supporting information online at

 

 

Prions causing neurodegeneration: A unifying etiology and the quest for therapeutics
 
Stanley B Prusiner University of California, Institute for Neurodegenerative Diseases; San Francisco, CA, USA
 
Mounting evidence argues that prions feature in the pathogenesis of many, if not all, neurodegenerative diseases. Such disorders include Alzheimer’s, Parkinson’s, Lou Gehrig’s and Creutzfeldt-Jakob diseases as well as the frontotemporal dementias. In each of these illnesses, aberrant forms of a particular protein accumulate as pathological deposits referred to as amyloid plaques, neurofibrillary tangles, Lewy bodies, as well as glial cytoplasmic and/or nuclear inclusions. The heritable forms of the neurodegenerative diseases are often caused by mutations in the genes encoding the mutant, prion proteins that accumulate in the CNS of patients with these fatal disorders. The late onset of the inherited neurodegenerative diseases seems likely to be explained by the protein quality control systems being less efficient in older neurons and thus, more permissive for prion accumulation. To date, there is not a single drug that halts or even slows one neurodegenerative disease.
 
References
 
Prusiner SB. Biology and genetics of prions causing neurodegeneration. Annu Rev Genet 2013; 47:601-23; PMID:24274755; http://dx.doi.org/10.1146/ annurev-genet-110711-155524
 
Jucker M, Walker LC. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 2013; 501:45-51; PMID:24005412; http://dx.doi. org/10.1038/nature12481
 
 
 
Wednesday, April 2, 2014
 
Do prions cause Parkinson disease?: The evidence accumulates (pages 331–333)

 
http://betaamyloidcjd.blogspot.com/2014/04/do-prions-cause-parkinson-disease.html

 

Tuesday, November 26, 2013

 

Transmission of multiple system atrophy prions to transgenic mice

 


 


 


 

 

 

TSS

Wednesday, April 2, 2014

Do prions cause Parkinson disease?: The evidence accumulates (pages 331–333)



C. Warren Olanow

Article first published online: 24 FEB 2014 | DOI: 10.1002/ana.24098
 
“Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.” –Winston Churchill
 
snip...
 
A body of evidence now suggest that Parkinson disease (PD) may also be a prion disorder, and that z-synuclein may be a prion...
 
 
 
 
 
 
Sunday, February 10, 2013
 
Parkinson's Disease and Alpha Synuclein: Is Parkinson's Disease a Prion-Like Disorder?
 
 
 
Wednesday, September 21, 2011
 
PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)
 
 
 
Wednesday, January 5, 2011
 
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
 
David W. Colby1,* and Stanley B. Prusiner1,2
 
 
 
 
Friday, September 3, 2010
 
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
 
 
 
 
Wednesday, May 16, 2012
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
Background
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy disease have both been around a long time, and was discovered in or around the same time frame, early 1900’s. Both diseases are incurable and debilitating brain disease, that are in the end, 100% fatal, with the incubation/clinical period of the Alzheimer’s disease being longer (most of the time) than the TSE prion disease. Symptoms are very similar, and pathology is very similar.
 
Methods
 
Through years of research, as a layperson, of peer review journals, transmission studies, and observations of loved ones and friends that have died from both Alzheimer’s and the TSE prion disease i.e. Heidenhain Variant Creutzfelt Jakob Disease CJD.
 
Results
 
I propose that Alzheimer’s is a TSE disease of low dose, slow, and long incubation disease, and that Alzheimer’s is Transmissible, and is a threat to the public via the many Iatrogenic routes and sources. It was said long ago that the only thing that disputes this, is Alzheimer’s disease transmissibility, or the lack of. The likelihood of many victims of Alzheimer’s disease from the many different Iatrogenic routes and modes of transmission as with the TSE prion disease.
 
Conclusions
 
There should be a Global Congressional Science round table event set up immediately to address these concerns from the many potential routes and sources of the TSE prion disease, including Alzheimer’s disease, and a emergency global doctrine put into effect to help combat the spread of Alzheimer’s disease via the medical, surgical, dental, tissue, and blood arena’s. All human and animal TSE prion disease, including Alzheimer’s should be made reportable in every state, and Internationally, WITH NO age restrictions. Until a proven method of decontamination and autoclaving is proven, and put forth in use universally, in all hospitals and medical, surgical arena’s, or the TSE prion agent will continue to spread. IF we wait until science and corporate politicians wait until politics lets science _prove_ this once and for all, and set forth regulations there from, we will all be exposed to the TSE Prion agents, if that has not happened already.
 
end...tss
 
SEE FULL TEXT AND SOURCE REFERENCES ;
 
Wednesday, May 16, 2012
 
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
 
Proposal ID: 29403
 
 
Tuesday, November 26, 2013
 
Transmission of multiple system atrophy prions to transgenic mice
 
 
 
 
 
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. 93/01.05/4.1
 
 
 
 
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/YdeS 92/11.4/1.2
 
 
 
 
BSE101/1 0136
 
IN CONFIDENCE
 
CMO
 
From: Dr J S Metters DCMO
 
4 November 1992
 
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
 
 
 
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
 
 
 
IATROGENIC
 
 
all iatrogenic cjd is, is sporadic CJD, until route and source of the iatrogenic event that took place, is detected, documented, placed in the academic domain as fact, and recorded, which happens very seldom due to a lot of factors, besides the incubation period, and that be mainly industry. kind of like asbestos and tobacco and the industry there from, they knew in the early 1900’s that they both were killing, and they both had long incubation, and somebody chose not to do anything about if for decades and decades. kind of like what we have here with the TSE prion disease. $$$
 
> In 12 of 15 hospitals with neurosurgical incidents, a decision was made to notify patients of their potential exposure.
 
SO, X number of patients, from 3 hospitals, where
 
''exposure to potentially CJD-contaminated instruments ''
 
took place on these patients, the final decision NOT to tell those folks about the potential exposure to the CJD TSE prion
 
insane, thus, the TSE prion agent continues to spread. ...please see further comments here ;
 
 
 
Tuesday, April 01, 2014
 
Questions linger in U.S. CJD cases 2005, and still do in 2014
 
 
 
 
TSS