Thursday, July 30, 2015

Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes

Journal of Neuropathology & Experimental Neurology:


Post Author Corrections: July 29, 2015


doi: 10.1097/NEN.0000000000000228


Original Article: PDF Only


Prion Disease Induces Alzheimer Disease-Like Neuropathologic Changes.


Tousseyn, Thomas MD, PhD; Bajsarowicz, Krystyna MS; Sánchez, Henry MD; Gheyara, Ania MD, PhD; Oehler, Abby BS; Geschwind, Michael MD, PhD; DeArmond, Bernadette MD, MPH; DeArmond, Stephen J. MD, PhD




We examined the brains of 266 patients with prion disease (PrionD) and found that 46 patients (17%) had Alzheimer disease (AD)-like changes. To explore potential mechanistic links between PrionD and AD, we exposed human brain aggregates (BrnAggs) to a brain homogenate from a patient with sporadic Creutzfeldt-Jakob disease and found that neurons in human BrnAggs produced many [beta]-amyloid (A[beta]; A[beta]42) inclusions, whereas uninfected control-exposed human BrnAggs did not. Western blot analysis of 20 pooled Creutzfeldt-Jakob disease-infected BrnAggs verified A[beta]42 levels higher than those in controls. We next examined the CA1 region of the hippocampus from 14 patients with PrionD and found that 5 patients had low levels of scrapie-associated prion protein (PrPSc), many A[beta]42 intraneuronal inclusions, low apolipoprotein E-4 (APOE-4), and no significant nerve cell loss. Seven patients had high levels of PrPSc, low A[beta]42, high APOE-4, and 40% nerve cell loss, suggesting that APOE-4 and PrPSc together cause neuron loss in PrionD. There were also increased levels of hyperphosphorylated tau protein (H[tau]) and H[tau]-positive neuropil threads and neuron bodies in both PrionD and AD groups. The brains of 6 age-matched control patients without dementia did not contain A[beta]42 deposits; however, there were rare H[tau]-positive threads in 5 controls, and 2 controls had few H[tau]-positive nerve cell bodies. We conclude that PrionD may trigger biochemical changes similar to those triggered by AD and suggest that PrionD is a disease involving PrPSc, A[beta]42, APOE-4, and abnormal tau.


(C) 2015 by American Association of Neuropathologists, Inc.



Int. J. Exp. Path. (1993) 74, 441-454


Evidence for the experimental transmission of cerebral f-amyloidosis to primates




*Division of Psychiatry, Clinical Research Centre, Harrow; tDepartment of Neuropathology, Institute of Neurology, National Hospital, Queen Square, London WC1N 3BG;


4MRC Department of Neuropathology, Runwell Hospital, Wickford, Essex SS1 17QE, UK


Received for publication 8 March 1993


Accepted for publication 21 May 1993


Summary. The brains of three marmosets (Callithrix jacchus) injected intracerebrally 6-7 years earlier with brain tissue from a patient with early onset Alzheimer's disease were found to contain moderate numbers of amyloid plaques with associated argyrophilic dystrophic neurites and cerebral amyloid angiopathy but no neurofibrillary tangles. The plaques and vascular amyloid stained positively with antibodies to fl(A4)-protein. The brains of three age-matched control marmosets from the same colony did not show these neuropathological features. The brain of one of two marmosets injected with brain tissue from a patient with prion disease with concomitant fl-amyloid plaques and cerebral amyloid angiopathy also showed fl-amyloid plaques and angiopathy but no spongiform encephalopathy. An occasional plaque was found in the brains of two of four marmosets injected with brain tissue from three elderly patients with age-related pathology, two of whom had an additional diagnosis of possible prion disease. Neither plaques nor cerebral amyloid angiopathy were found in six other marmosets who were older than the injected animals, in 12 further marmosets who were slightly younger but who had been injected several years previously with brain tissue which did not contain ,B-amyloid, or in 10 younger marmosets who had been subjected to various neurosurgical procedures. These results suggest that cerebral ,B-amyloidosis may be induced by the introduction of exogenous amyloid fl-protein.




Despite some alarmist claims, the occurrence of prion disease with none of the hallmarks of prion disease and all of the hallmarks of another neurodegenerative disease is 'imagined' (Brown et a/. 1993). There are no differential clinical or neuropathological features to suggest that case 1 had a prion disease rather than AD and the lack of a characteristic EEG, myoclonus, SE or PrP-staining plaques argue against a diagnosis of prion disease. Although ,B-amyloid plaques have been found in prion disease, the majority of these occur in elderly patients (Roberts et a/. 1988). Occasional concomitant ,B-amyloidosis has been found in prion disease (as in case 2; Watanabe & Duchen 1993) but in these cases the degree of ,B-amyloidosis is not as extensive as that seen in case 1 which was extremely severe. Neurofibrillary tangles are an unusual feature in prion disease and, when they do occur, tend to be localized to the hippocampus. However, in the Indiana kindred, which does have a large number of NFT and plaques and a PrP198 mutation (Dlouhy et al. 1992), the plaques stain with anti-PrP as well as anti-,B-amyloid antibodies (Bugiani et a/. 1993).


Thus the pathology of case 1 was typical of AD and we conclude that the amyloidosis of that and the other brains ,B-amyloid has been transmitted to marmosets by intracerebral injection.


Keywords: fJ(A4)-amyloid, senile plaques, primates, Alzheimer's disease



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 ***



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




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.




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.




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.




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.






Wednesday, May 16, 2012


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


Proposal ID: 29403



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.




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




Dr McGovern From: Dr A Wight Date: 5 January 1993 Copies: Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray




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




5 NOV 1992 CMO From: Dr J S Metters DCMO 4 November 1992




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






From: Dr J S Metters DCMO


4 November 1992





CJD1/9 0185


Ref: 1M51A




From: Dr. A Wight Date: 5 January 1993




Dr Metters Dr Skinner Dr Pickles Dr Morris Mr Murray





***PRION2015 Ft. Collins***


Alzheimer’s disease


*** P.34: Preliminary study of Alzheimer’s disease transmission to bank vole ***


Guido Di Donato1, Geraldina Riccardi1, Claudia D’Agostino1, Flavio Torriani1, Maurizio Pocchiari2, Romolo Nonno1, Umberto Agrimi1, and Michele Angelo Di Bari1


1Department of Food Safety and Veterinary Public Health Istituto Superiore di Sanit a, Rome, Italy; 2Department of Cellular Biology and Neuroscience; Istituto Superiore di Sanit a, Rome, Italy


Extensive experimental findings indicate that prion-like mechanisms underly the pathogenesis of Alzheimer disease (AD). Transgenic mice have been pivotal for investigating prionlike mechanisms in AD, still these models have not been able so far to recapitulate the complex clinical-pathological features of AD. Here we aimed at investigating the potential of bank vole, a wild-type rodent highly susceptible to prions, in reproducing AD pathology upon experimental inoculation.


Voles were intracerebrally inoculated with brain homogenate from a familial AD patient. Animals were examined for the appearance of neurological signs until the end of experiment (800 d post-inoculation, d.p.i.). Brains were studied by immunohistochemistry for pTau Prion 2015 Poster Abstracts S29 (with AT180 and PHF-1 antibodies) and b-amyloid (4G8).


Voles didn’t show an overt clinical signs, still most of them (11/16) were found pTau positive when culled for intercurrent disease or at the end of experiment. Interestingly, voles culled as early as 125 d.p.i. already showed pTau aggregates. Deposition of pTau was similar in all voles and was characterized by neuropil threads and coiled bodies in the alveus, and by rare neurofibrillary tangles in gray matter. Conversely, b-amyloid deposition was rather rare (2/16). Nonetheless, a single vole showed the contemporaneous presence of pTau in the alveus and a few Ab plaque-like deposits in the subiculum. Uninfected age-matched voles were negative for pTau and Ab.


*** These findings corroborate and extend previous evidences on the transmissibility of pTau and Ab aggregation. Furthermore, the observation of a vole with contemporaneous propagation of pTau and Ab is intriguing and deserves further studies.




P.155: Quantitative real-time analysis of disease specific tau amyloid seeding activity


Davin Henderson and Edward Hoover Prion Research Center; College of Veterinary Medicine and Biomedical Sciences; Colorado State University; Fort Collins, CO USA


A leading hypothesis for the cause of neurodegenerative diseases is the templated misfolding of cellular proteins to an amyloid state. Spongiform encephalopathies were the first diseases discovered to be caused by a misfolded amyloid-rich protein. It is now recognized that the major human neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and chronic traumatic encephalopathy (CTE), also are associated with amyloid formation. Moreover, AD and PD amyloids have been shown competent to transmit disease in experimental animal models, suggesting shared mechanisms with traditional prion diseases. Sensitive detection of prion disease has been advanced by in vitro amplification of low levels of disease specific amyloid seeds, e.g. serial protein misfolding amplification (sPMCA), amyloid seeding (ASA) and real-time quaking induced conversion (RT-QuIC), thereby replicating the disease process in vitro. In addition, measurement of the amyloid formation rate can estimate the level of disease-associated seed by using methods analogous to quantitative polymerase chain reaction (qPCR). In the present work, we apply these principles to show that seeding activity of in vitro generated amyloid tau and AD brain amyloid tau can be readily detected and quantitated.




P.83: Gerstmann-Str€aussler-Scheinker disease with F198S mutation: Selective propagation of PrPSc and pTau upon inoculation in bank vole


Michele Angelo Di Bari1, Romolo Nonno1, Laura Pirisinu1, Claudia D’Agostino1, Geraldina Riccardi1, Guido Di Donato1, Paolo Frassanito1, Bernardino Ghetti2, Pierluigi Gambetti3, and Umberto Agrimi1


1Department of Veterinary Public Health and Food Safety; Istituto Superiore di Sanit a; Rome, Italy;


2Indiana University-Purdue University Indianapolis; Department of Pathology and Laboratory Medicine; Indianapolis, IN USA; 3Case Western Reserve University; Cleveland, OH USA


Gerstmann-Str€aussler-Scheinker disease with F198S mutation (GSS-F198S) is characterized by the presence of PrP amyloid plaques as well as neurofibrillary tangles with abnormally-phosphorylated tau protein (pTau) in the brain. The relationship between tau protein and PrP in the pathogenesis of GSS-F198S is unknown. In a previous study, we inoculated intracerebrally 2 GSS-F198S cases in 2 lines of voles carrying either methionine (Bv109M) or isoleucine (Bv109I) at codon 109 of PrP. GSS-F198S transmitted rather efficiently to Bv109I, but not to Bv109M.


Here we investigated the presence of pTau, as assessed by immunohistochemistry with anti-pTau antibodies AT180 and PHF-1, in the same voles previously inoculated with GSSF198S. Among these voles, most Bv109I showed clinical signs after short survival times (»150 d.p.i.) and were positive for PrPSc. The remaining Bv109I and all Bv109M survived for longer times without showing prion-related pathology or detectable PrPSc. All Bv109I which were previously found PrPSc-positive,


S54 Prion 2015 Poster Abstracts


were immunonegative for pTau deposition. In contrast, pTau deposition was detected in 16/20 voles culled without clinical signs after long survival times (225–804 d.p.i.). pTau deposition was characterized by neuropil threads and coiled bodies in the alveus, and was similar in all voles analyzed.


These findings highlight that pTau from GSS-F198S can propagate in voles. Importantly, pTau propagation was independent from PrPSc, as pTau was only found in PrPSc-negative voles surviving longer than 225 d.p.i. Thus, selective transmission of PrPSc and pTau proteinopathies from GSS-F198S can be accomplished by experimental transmission in voles.




I3 Aβ Strains and Alzheimer’s Disease


Lary Walker Emory University, Atlanta, GA, USA


An essential early event in the development of Alzheimer’s disease is the misfolding and aggregation of Aβ. Enigmatically, despite the extensive deposition of human-sequence Aβ in the aging brain, nonhuman primates do not develop the full pathologic or cognitive phenotype of Alzheimer’s disease, which appears to be unique to humans. In addition, some humans with marked Aβ accumulation in the brain retain their cognitive abilities, raising the question of whether the pathogenicity of Aβ is linked to the molecular features of the misfolded protein. I will present evidence for strain-like molecular differences in aggregated Aβ between humans and nonhuman primates, and among end-stage Alzheimer patients. I will also discuss a case of Alzheimer’s disease with atypical Aβ deposition to illustrate heterogeneity in the molecular architecture of Aβ assemblies, and how this variability might influence the nature of the disease. As in the case of prion diseases, strain-like variations in the molecular architecture of Aβ could help to explain the phenotypic variability in Alzheimer’s disease, as well as the distinctively human susceptibility to the disorder.


This research was conducted in collaboration with Harry LeVine, Rebecca Rosen, Amarallys Cintron, David Lynn, Yury Chernoff, Anil Mehta and Mathias Jucker and colleagues. Supported by AG040589, RR165/OD11132, AG005119, NS077049, the CART Foundation and MetLife.




I5 Pathogenic properties of synthetically generated prions


Jiyan Ma Van Andel Research Institute, Grand Rapids, Michigan, USA


Synthetically generating prions with bacterially expressed recombinant prion protein (recPrP) strongly supports the prion hypothesis. Yet, it remains unclear whether the pathogenic properties of synthetically generated prions (rec-Prion) fully recapitulate those of naturally occurring prions. A series of analyses including intracerebral and intraperitoneal transmissions of rec-Prion in wild-type mice were performed to determine the characteristics of rec-Prion induced diseases. Results from these analyses demonstrated that the rec-Prion exhibits the same pathogenic properties with naturally occurring prions, including a titratable infectivity that can be determined by endpoint titration assays, capability of transmitting prion disease via routes other than the direct intra-cerebral inoculation, causing ultra-structural lesions that are specific to prion disease, and sharing a similar manner of visceral dissemination and neuroinvasion with naturally occurring scrapie and chronic wasting disease. These findings confirmed that the disease caused by rec-Prion in wild-type mice is bona fide prion disease or transmissible spongiform encephalopathiges, and the rec-Prion contains similar pathogenic properties as naturally occurring prions.


I6 Transmissible protein toxins in neurodegenerative disease


Jacob Ayers, David Borchelt University of Florida, Gainesville, FL, USA


Amyotrophic lateral sclerosis (ALS) is an obvious example of neurodegenerative disease that seems to spread along anatomical pathways. The spread of symptoms from the site of onset (e.g. limb) to the respiratory musculature drives the rate of disease progression. In cognitive disorders, such as Alzheimer’s disease, one can find similarly find evidence of spreading dysfunction and pathology. One mechanism to account for this spread of disease from one neural structure to another is by evoking prion-like propagation of a toxic misfolded protein from cell to cell. Recent studies in animals that model aspects of Alzheimer’s Disease, Parkinson’s Disease, and Tauopathy, have bolstered the arguments in favor of prion-like, although in most of these models the mice do not develop overt “clinical” symptoms. Recently, Jacob Ayers demonstrated that the symptoms of ALS can be transmitted from a strain of mice that expresses mutant SOD1-G93A at high levels to a second transgenic strain that expresses mutant SOD1 at low, nontoxic, levels. This model showed many prion-like features including evidence of host-adaptation (earlier and more penetrant disease upon second passage). Interestingly, homogenates from paralyzed mice expressing the G37R variant of SOD1 transmitted poorly, a finding suggestive that different SOD1 variants may exhibit strain-like properties. These “ i n d u c i b l e ” m o d e l s o f h u m a n neurodegenerative disease enable the generation of models that do not require extraordinary levels of transgene expression and provide a more precise means of initiating the disease process, advances that may translate into more predictive pre-clinical models.




P188 Transmission of amyloid pathology by peripheral administration of misfolded Aβ


Javiera Bravo-Alegria1 ,2, Rodrigo Morales2, Claudia Duran-Aniotz3, Claudio Soto2 1University of Los Andes, Santiago, Chile, 2Mitchell Center for Alzheimer’s Disease and Related Brain Disorders, Department of Neurology, University of Texas Medical School, Houston, Texas, USA, 3University of Chile, Santiago, Chile


Misfolding and aggregation of Amyloid-β (Aβ) is one of the primary events involved in the pathogenesis of Alzheimer's disease (AD). Recently, it has been proposed that Aβ aggregates can transmit and spread the pathology following a prion-like mechanism. Prions can be exogenously transmitted by many different routes of administration. In the case of Aβ, previous studies showed that intraperitoneal (i.p.) injection of seeds can accelerate cerebral amyloidosis in mouse models. However, other potential routes have not yet been studied. The goal of this work was to assess whether Aβ amyloidosis can be seeded in the brain of a transgenic mouse model of AD by peripheral administration of misfolded particles.


Young tg2576 animals (50 days old) were inoculated with a pool of brain extract coming from old Tg2576 animals (10%w/v) by different routes: i.p. (100μL), eye drops (5μL each eye, 3 times), intramuscular (i.m., 50μL), and per os (p.o., 1000μL). Animals were sacrificed at 300 days old, and brain samples were analyzed for amyloid pathology by IHC and ELISA.


The i.p., i.m., and eye drops administration of Aβ seeds significantly accelerated pathological features in tg2576. Regardless of the higher volume administered, p.o. treated animals did not show any pathological changes when compared to untreated controls. Differences in the proportion of diffuse, core and vascular deposition was observed within experimental groups. Our data show that peripheral administration of Aβ seeds could accelerate pathological changes in the brain and suggest that an orchestrated cross-talk between the brain and peripheral tissues occurs in AD.






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 ;



Tuesday, June 30, 2015


PRION2015 Alzheimer’s disease



Tuesday, June 30, 2015


visual variant of Alzheimer’s disease VVAD vs Heidenhain Variant Creutzfeldt Jakob Disease hvCJD





*** RE-P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study


***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. ***


ran across an old paper from 1984 ;


***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent. ***



***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD...see;


P.164: Blood transmission of prion infectivity in the squirrel monkey: The Baxter study


Paul Brown1, Diane Ritchie2, James Ironside2, Christian Abee3, Thomas Kreil4, and Susan Gibson5 1NIH (retired); Bethesda, MD USA; 2University of Edinburgh; Edinburgh, UK; 3University of Texas; Bastrop, TX USA; 4Baxter Bioscience; Vienna, Austria; 5University of South Alabama; Mobile, AL USA


Five vCJD disease transmissions and an estimated 1 in 2000 ‘silent’ infections in UK residents emphasize the continued need for information about disease risk in humans. A large study of blood component infectivity in a non-human primate model has now been completed and analyzed. Among 1 GSS, 4 sCJD, and 3 vCJD cases, only GSS leukocytes transmitted disease within a 5–6 year surveillance period. A transmission study in recipients of multiple whole blood transfusions during the incubation and clinical stages of sCJD and vCJD in ic-infected donor animals was uniformly negative. These results, together with other laboratory studies in rodents and nonhuman primates and epidemiological observations in humans, ***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD. The issue of decades-long incubation periods in ‘silent’ vCJD carriers remains open.




***suggest that blood donations from cases of GSS (and perhaps other familial forms of TSE) carry more risk than from vCJD cases, and that little or no risk is associated with sCJD...see;


Wednesday, December 11, 2013


*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***







From: Terry S. Singeltary Sr.


Sent: Saturday, November 15, 2014 9:29 PM


To: Terry S. Singeltary Sr.

















Friday, January 10, 2014


vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ??? Greetings Friends, Neighbors, and Colleagues,


vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???


Confucius is confused again.


I was just sitting and thinking about why there is no genetic link to some of these TSE prion sGSS, sFFi, and it’s really been working on my brain, and then it hit me today.


what if, vpspr, sgss, sffi, TSE prion disease, was a by-product from iatrogenic gss, ffi, familial type prion disease ???


it could explain the cases of no genetic link to the gss, ffi, familial type prion disease, to the family.


sporadic and familial is a red herring, in my opinion, and underestimation is spot on, due to the crude prehistoric diagnostic procedures and criteria and definition of a prion disease.


I say again, what if, iatrogenic, what if, with all these neurological disorders, with a common denominator that is increasingly showing up in the picture, called the prion.


I urge all scientist to come together here, with this as the utmost of importance about all these neurological disease that are increasingly showing up as a prion mechanism, to put on the front burners, the IATROGENIC aspect and the potential of transmission there from, with diseases/disease??? in question.


by definition, could they be a Transmissible Spongiform Encephalopathy TSE prion type disease, and if so, what are the iatrogenic chances of transmission?


this is very important, and should be at the forefront of research, and if proven, could be a monumental breakthrough in science and battle against the spreading of these disease/diseases.


the US National Library of Medicine National Institutes of Health pub-med site, a quick search of the word SPORADIC will give you a hit of 40,747. of those, there are a plethora of disease listed under sporadic. sporadic simply means (UNKNOWN).



the US National Library of Medicine National Institutes of Health pub-med site, a quick search of the word FAMILIAL will give you a hit of 921,815. of those, there are a plethora of disease listed under familial.



again, sporadic and familial is a red herring, in my opinion.


also, in my opinion, when you start have disease such as sporadic Fatal Familial Insomnia, (and or sporadic GSS, or the VPSPr type prion disease), and there is NO familial genetic linkage to the family of the diseased, I have serious questions there as to a familial type disease, and thus, being defined as such.


*UPDATE* NOVEMBER 16, 2014 vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ??? Friday, January 10, 2014


Greetings again Friends, Neighbors, and Colleagues,


snip...see ;



Wednesday, January 28, 2015


Another new prion disease: relationship with central and peripheral amyloidoses



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




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




Tuesday, October 4, 2011


Molecular Psychiatry


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


De novo induction of amyloid-ß deposition in vivo


Our results suggest that some of the typical brain abnormalities associated with AD can be induced by a prion-like mechanism of disease transmission through propagation of protein misfolding. These findings may have broad implications for understanding the molecular mechanisms responsible for the initiation of AD, and may contribute to the development of new strategies for disease prevention and intervention. Keywords: amyloid; prion; protein misfolding; disease transmission



see more here ;




Friday, September 3, 2010


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






... a TSE is found that is linked to Alzheimer’s disease.



Wednesday, July 15, 2015


*** Additional BSE TSE prion testing detects pathologic lesion in unusual brain location and PrPsc by PMCA only, how many cases have we missed? ***



Diagnosis and Reporting of Creutzfeldt-Jakob Disease


Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA


Diagnosis and Reporting of Creutzfeldt-Jakob Disease


To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.


Terry S. Singeltary, Sr Bacliff, Tex


1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.

























iatrogenic, what if ???


Terry S. Singeltary Sr.