August 19, 2024
Expanding the Prion Paradigm to Include Alzheimer and Parkinson DiseasesCarlo Condello, PhD1,2; David Westaway, PhD1,2; Stanley B. Prusiner, MD1,2
Author Affiliations
1Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco
2Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco
JAMA Neurol. Published online August 19, 2024. doi:10.1001/jamaneurol.2024.2464
In 1968, Clarence Gibbs, Carleton Gajdusek, and coworkers reported the experimental transmission of Creutzfeldt-Jakob disease (CJD) from humans to apes. Subsequently, research found that scrapie in sheep and CJD in people were caused by a misfolded protein, PrP, and led to the introduction of the term prion to distinguish these pathogens from viruses, bacteria, protozoa, and helminths, all of which replicate through a nucleic acid genome.1 The related discovery that the prions causing scrapie and CJD were host-encoded by the PRNP gene led to a series of investigations as to how CJD could manifest as a sporadic illness, an inherited disorder, or a transmissible malady. Recent studies now argue that amyloid-β (Aβ) peptide, tau protein, and α-synuclein protein are chemically distinct prions that all can adopt pathogenic, self-propagating conformations; these other varieties of prions (ie, those not based on misfolded PrP) result in neurodegenerative diseases such as Alzheimer disease (AD), multiple system atrophy, and Parkinson disease.2,3 With these advances, it would be prudent to abandon the quest for an alternate word to supplant prion and to discard terms such as prion-like, which denotes a level of uncertainty that is no longer justified.
https://jamanetwork.com/journals/jamaneurology/article-abstract/2822641
Singeltary Comment at very bottom of this Nature publishing, takes a while to load...terry
https://www.nature.com/articles/nature15369#article-comments
https://www.nature.com/articles/nature15369#article-comments
Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?
Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)
snip...see full Singeltary Nature comment here;
Alzheimer's disease
let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...
Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
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
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d
The only tenable public line will be that "more research is required’’ <<<
possibility on a transmissible prion remains open<<<
O.K., so it’s about 23 years later, so somebody please tell me, when is "more research is required’’ enough time for evaluation ?
Re-Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Nature 525, 247?250 (10 September 2015) doi:10.1038/nature15369 Received 26 April 2015 Accepted 14 August 2015 Published online 09 September 2015 Updated online 11 September 2015 Erratum (October, 2015)
snip...see full Singeltary Nature comment here;
Alzheimer's disease
let's not forget the elephant in the room. curing Alzheimer's would be a great and wonderful thing, but for starters, why not start with the obvious, lets prove the cause or causes, and then start to stop that. think iatrogenic, friendly fire, or the pass it forward mode of transmission. think medical, surgical, dental, tissue, blood, related transmission. think transmissible spongiform encephalopathy aka tse prion disease aka mad cow type disease...
Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
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
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
https://journals.plos.org/plosone/article/comment?id=10.1371/annotation/933cc83a-a384-45c3-b3b2-336882c30f9d
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.
https://pubmed.ncbi.nlm.nih.gov/6758661/
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.
https://pubmed.ncbi.nlm.nih.gov/6758661/
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
http://web.archive.org/web/20090506012455/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
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
http://web.archive.org/web/20090506012455/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/YdeS 92/11.4/1.2
https://web.archive.org/web/20170126060344/http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight Date: 5 January 1993
Copies:
Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
''on the possible transmissibility of Alzheimer's''
9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly
(1) concerning a farmer with CJD who had BSE animals,
(2) on the possible transmissibility of Alzheimer's and
(3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.
https://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf
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
https://web.archive.org/web/20170126060344/http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
From: Dr. A Wight Date: 5 January 1993
Copies:
Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
''on the possible transmissibility of Alzheimer's''
9. Whilst this matter is not at the moment directly concerned with the iatrogenic CJD cases from hgH, there remains a possibility of litigation here, and this presents an added complication. There are also results to be made available shortly
(1) concerning a farmer with CJD who had BSE animals,
(2) on the possible transmissibility of Alzheimer's and
(3) a CMO letter on prevention of iatrogenic CJD transmission in neurosurgery, all of which will serve to increase media interest.
https://web.archive.org/web/20040315075058/http://www.bseinquiry.gov.uk/files/yb/1992/12/16005001.pdf
Alzheimer’s disease and Transmissible Spongiform Encephalopathy prion disease, Iatrogenic, what if ?
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Posted by flounder on 05 Nov 2014 at 21:27 GMT
Terry S. Singeltary Sr.
