PRION 2025 RIO DE JANEIRO
Thank you PRION 2025 RIO DE JANEIRO, and all the Scientists et al that were involved, a well put together Program, Presentation, Papers.
heres a few abstracts…kind regards terry
PRION 2025 RIO DE JANEIRO
Zoonotic potential of ruminant prion diseases: from primate to mice
Comoy, Emmanuel 1Mikol, Jacqueline 1Delmotte, Jérome 1Andreoletti, Olivier 2Deslys, Jean-Philippe 1 Vol 1, 2025 - 328779 Abstract Prion 2025
Abstract Introduction: previous experiments reported the transmission of certain isolates of sheep scrapie to humanized mice and non-human primates, supporting an unexpected zoonotic potential of an animal disease known from centuries. For some of them, transmission to rodents were observed only after an intermediate passage in transgenic mice expressing bovine PrP (Tg110), this sequential transmission being considered as a model of the hypothesis of a scrapie origin of BSE.
Objectives: we aim to complete this second part of experiments in our non-human primate model that is known as sensitive to human and cattle prion strains.
Methods: cynomolgus macaques were intracerebrally exposed to different scrapie isolates directly issued from sheep or after passages in Tg110transgenic mice, and post mortem analysed using conventional biochemical and histological techniques. Successive transmissions to mice expressing ovine, bovine or macaque PrP were performed.
Results/Discussion: These new macaque studies confirmed that scrapie can be transmitted from certain sheep isolates to non-human primate after extended incubation periods (10 years), whereas after passage in Tg110 mice transmission may occur with two-fold shorter incubation periods. These resulting diseases and BSE will be compared according to their respective biochemical, pathological and transmission features. The combined observation of unexpected immunohistological labelling with reverse yet unpublished experiments of BSE passage on small ruminants as intermediate hosts, underline the impact of the host species on the phenotype and the zoonotic potential of animal prion diseases, enforcing the pivotal role played by cattle.
https://proceedings.science/prion-2025/papers/zoonotic-potential-of-ruminant-prion-diseases-from-primate-to-mice?lang=en
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
PRION 2025 RIO DE JANEIRO
“ These new macaque studies confirmed that scrapie can be transmitted from certain sheep isolates to non-human primate after extended incubation periods (10 years), whereas after passage in Tg110 mice transmission may occur with two-fold shorter incubation periods.”
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Btrack.title.en%5D%5B0%5D=Animal%20prion%20diseases
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=Scrapie
https://proceedings.science/prion-2025/papers
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
CWD prion strain variation modeled in the lab and identified in natural cases
SOTO, PAULINA 1Benavente, Maria 2Kramm, Carlos 2Stimming, Tucker 2Bravo-Risi, Francisca 3Pritzkow, Sandra 2Lyon, Adam 2Reed, J Hunter 4Soto, Claudio 2Morales, Rodrigo 5 Vol 1, 2025 - 328841 Abstract Prion 2025
Abstract Introduction: Chronic Wasting Disease (CWD) is a prion disease affecting cervids. It is characterized by distinct prion strains, which can influence transmission rates and disease phenotypes. In white-tailed deer, polymorphism at codon 96 of the PRNP gene (glycine (G) or serine (S)) is associated with differential susceptibility to CWD. The 96SS genotype has been consider “protective”; however, the potential for prion adaptation across deer PrP polymorphic variants remains unclear. Worrisomely, current surveillance strategies do not consider the identification of CWD prion strains, a fact that may contribute to CWD epidemiology.
Methods: We modeled inter-polymorphic prion conversion and demonstrate that prions can efficiently adapt in 96SS hosts with infectious properties like those in classical CWD strains. To investigate this, CWD prions from 96GG and 96SS deer were propagated by PMCA using homologous and heterologous transgenic brain homogenates, resulting in four strain combinations: GG/GG, SS/GG, GG/SS, and SS/SS (donor/recipient). These were characterized biochemically and tested in Tg1536and Tg60 mice. As part of this project, four natural CWD prion isolates identified in screening/diagnostic practices were similarly analyzed.
Results and Discussion: All experimental strains showed biochemical differences, indicating structural divergence. In Tg1536 mice, all strains produced disease with full attack rates. In Tg60mice, few animals developed clinical signs, but all showed PrPSc and vacuolation. These results indicate that the PRNP polymorphism modulates disease progression but does not prevent infection. Natural isolates also showed biochemical and pathological diversity, demonstrating the existence of diverse prion strains circulating in the environment.
PRION 2025 RIO DE JANEIRO
“ These new macaque studies confirmed that scrapie can be transmitted from certain sheep isolates to non-human primate after extended incubation periods (10 years), whereas after passage in Tg110 mice transmission may occur with two-fold shorter incubation periods.”
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Btrack.title.en%5D%5B0%5D=Animal%20prion%20diseases
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=Scrapie
https://proceedings.science/prion-2025/papers
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
TWO UNEXPECTED CASES OF VARIABLY PROTEASE SENSITIVE PRIONOPATHY PRESENTING WITH A MOTOR NEURON/FRONTOTEMPORAL DEMENTIA SYNDROME IN A SMALL REGION IN NORTHERN SPAIN IDENTIFIED WITHIN ONE YEAR
Erro, María Elena 1Jericó, Ivonne 1Zelaya, María Victoria 2Caballero, Cristina 2García-Amigot, Fermín 3Gordoa, Javier Sánchez Ruiz de 1Serra, Anika Simonovska 4Ferrer, Isidre 5Castilla, Joaquín 6Gelpi, Ellen 4 Vol 1, 2025 - 329810 Abstract Prion 2025
Abstract Introduction
Variably protease-sensitive prionopathy (VPSPr) is a very rare sporadic prion disease.
Objective
To describe clinical, biochemical, and neuropathological findings of two new patients with VPSPr presenting with a motor-neuron/frontotemporal dementia syndrome.
Methods
Clinical evaluation, genetic analysis, postmortem neuropathological examination and biochemical analyses of the cellular prion protein (PrPsc).
Results
The patients were two men from unrelated families with an age at onset of 57 and 74 years. Mean disease duration was 46 and 67 months, respectively. Both presented with a motor-neuron syndrome compatible with primary lateral sclerosis with frontotemporal dementia. Neuropathology revealed a similar phenotype in both with mild spongiform change, neuronal loss and gliosis in fronto-temporal lobar distribution involving the motor system, and more severe affection of the thalamus. Peculiar PrPsc deposition pattern with extracellular fine-synaptic, fleecy and freckle-like accumulations, irregular patches, and micro-plaques as well as intracellular fine-granular and dotted aggregates in thalamic and motor-neurons, as described in VPSPr. Western blotting revealed PrPsc resistant proteolytic fragment after very mild digestion with PK, with clear non-glycosylated and mono-glycosylated bands of approximately 19 and 22-25 kDa respectively, and complete lack of di-glycosylated fragment. PRPN sequencing showed methionine-homozygosity (Met/Met) at codon 129 in both, and no mutations.
Conclusion
VPSPr is a very rare sporadic prion disorder which can manifest with motor neuron symptoms over several years in methionine-homozygous patients mimicking ALS/PLS and be associated with an FTD phenotype. These two cases contribute to broaden the knowledge about its clinical, biochemical, and neuropathological features, providing hints for its early recognition.
https://proceedings.science/prion-2025/papers/two-unexpected-cases-of-variably-protease-sensitive-prionopathy-presenting-with?lang=en
https://proceedings.science/prion-2025/papers
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
A critical perspective of Prion Disease surveillance in Brazil
BARBOSA, BRENO JOSE ALENCAR PIRES 1MONTENEGRO, MARIA LUIZA VASCONCELOS 2CUNHA, JOSE ERITON GOMES DA 3 Vol 1, 2025 - 326431 Abstract Prion 2025
Abstract Introduction: Prion Diseases (PrD) are a group of rapidly progressive dementias. Among its subtypes, Creutzfeldt-Jakob Disease (CJD) is the most common, affecting around 1 to 2 individuals per million inhabitants yearly. In 2005, Brazil's Ministry of Health (MH) initiated a surveillance program for CJD, creating a protocol to report the cases. Despite advances, the MH still struggles to make a reliable database to determine PrD profile in Brazil. Objectives: To understand the Brazilian PrD surveillance system. Methods: This is a retrospective and descriptive study based on the epidemiological records of CJD surveillance from 2005 to 2021 in the Ministry of Health's Epidemiological Bulletin published in 2022. Results/Discussion: 1.576 suspected cases of CJD were reported, concentrated in the Southeast, South and Northeast regions of Brazil. Among the notifications, the following age groups predominated: 55 to 74 years (60.2%), 45 to 54 years (15%), and 75 to 85 years (11.8%). Suspected cases were mainly represented by women (53.6%), white individuals (61.4%), and residents of urban areas (90%). In this period, the expected number of cases for the Brazilian population would be 3.200. Additionally to underreporting, the data shared by MH are limited due to the use of a database destined to mainly observe epidemic outbreaks and mismatches between official documents. Conclusion: Despite some progress since 2005, PrD surveillance in Brazil faces significant problems, due to the inaccurate treatment of these data and the lack of a specific database for CJD.
https://proceedings.science/prion-2025/papers/a-critical-perspective-of-prion-disease-surveillance-in-brazil?lang=en
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=Prion%20diseases
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
end…tss
i find this interesting…
PRION 2025 RIO DE JANEIRO
Zoonotic potential of ruminant prion diseases: from primate to mice
Comoy, Emmanuel 1Mikol, Jacqueline 1Delmotte, Jérome 1Andreoletti, Olivier 2Deslys, Jean-Philippe 1 Vol 1, 2025 - 328779 Abstract Prion 2025
Abstract Introduction: previous experiments reported the transmission of certain isolates of sheep scrapie to humanized mice and non-human primates, supporting an unexpected zoonotic potential of an animal disease known from centuries. For some of them, transmission to rodents were observed only after an intermediate passage in transgenic mice expressing bovine PrP (Tg110), this sequential transmission being considered as a model of the hypothesis of a scrapie origin of BSE.
Objectives: we aim to complete this second part of experiments in our non-human primate model that is known as sensitive to human and cattle prion strains.
Methods: cynomolgus macaques were intracerebrally exposed to different scrapie isolates directly issued from sheep or after passages in Tg110transgenic mice, and post mortem analysed using conventional biochemical and histological techniques. Successive transmissions to mice expressing ovine, bovine or macaque PrP were performed.
Results/Discussion: These new macaque studies confirmed that scrapie can be transmitted from certain sheep isolates to non-human primate after extended incubation periods (10 years), whereas after passage in Tg110 mice transmission may occur with two-fold shorter incubation periods. These resulting diseases and BSE will be compared according to their respective biochemical, pathological and transmission features. The combined observation of unexpected immunohistological labelling with reverse yet unpublished experiments of BSE passage on small ruminants as intermediate hosts, underline the impact of the host species on the phenotype and the zoonotic potential of animal prion diseases, enforcing the pivotal role played by cattle.
https://proceedings.science/prion-2025/papers/zoonotic-potential-of-ruminant-prion-diseases-from-primate-to-mice?lang=en
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
PRION 2025 RIO DE JANEIRO
“ These new macaque studies confirmed that scrapie can be transmitted from certain sheep isolates to non-human primate after extended incubation periods (10 years), whereas after passage in Tg110 mice transmission may occur with two-fold shorter incubation periods.”
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Btrack.title.en%5D%5B0%5D=Animal%20prion%20diseases
https://proceedings.science/prion-2025/papers?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=Scrapie
https://proceedings.science/prion-2025/papers
https://proceedings.science/prion-2025?prod_proceedings_papers%5BrefinementList%5D%5Bkeywords.en%5D%5B0%5D=PMCA
ARS Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies 2025
“ARS researchers in Ames, Iowa, showed that white-tailed deer sick with scrapie from sheep can infect other deer under conditions mimicking natural exposure. Furthermore, this work shows that CWD is difficult to differentiate from WTD infected with scrapie. WTD scrapie prions accumulate in the lymphoreticular system in a manner similar to CWD, meaning that environmental contamination may occur through feces, saliva, and other body fluids of scrapie affected WTD as has been shown for CWD. The presence of WTD infected with scrapie could confound mitigation efforts for chronic wasting disease. This information informs regulatory officials, the farmed cervid industry, and officials tasked with protecting animal health such as state Departments of Agriculture, Natural Resources, or Parks and Wildlife with regard to a disease similar to CWD but arising from sheep scrapie that could be present in WTD that have contact with scrapie affected sheep and/or goats.”
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
2025 Annual Report
Objectives
snip…
Accomplishments
1. 01 Determined that white-tailed deer (WTD) infected with scrapie from sheep can transmit the disease to other deer under conditions mimicking natural exposure. It has long been suggested that prion disease in deer (chronic wasting disease (CWD)) was caused by the prion agent from sheep. The prion disease that affects sheep, scrapie, has been recognized for hundreds of years. However, chronic wasting disease, a similar disease found in WTD, has only been recognized since the 1960s. ARS researchers in Ames, Iowa, showed that white-tailed deer sick with scrapie from sheep can infect other deer under conditions mimicking natural exposure. Furthermore, this work shows that CWD is difficult to differentiate from WTD infected with scrapie. WTD scrapie prions accumulate in the lymphoreticular system in a manner similar to CWD, meaning that environmental contamination may occur through feces, saliva, and other body fluids of scrapie affected WTD as has been shown for CWD. The presence of WTD infected with scrapie could confound mitigation efforts for chronic wasting disease. This information informs regulatory officials, the farmed cervid industry, and officials tasked with protecting animal health such as state Departments of Agriculture, Natural Resources, or Parks and Wildlife with regard to a disease similar to CWD but arising from sheep scrapie that could be present in WTD that have contact with scrapie affected sheep and/or goats.
2. 02 Showed that gene-targeted mice are capable of reproducing strain specific effects typically limited to natural host species of chronic wasting disease (CWD). CWD is a highly contagious disease of deer, elk, moose, and reindeer found in North America, South Korea, and Scandinavian countries that is caused by misfolded proteins called prions. CWD prions transmit through direct contact between infected animals, or through contaminated soil, grass, or water. All prion diseases exhibit progressive neurodegeneration and ultimately death. Scientists typically study CWD by injecting prions into susceptible animals' brains in lab experiments. Intracranial prion injections are favored because they typically produce shorter incubation periods and higher disease attack rates compared to natural infection. ARS researchers in Ames, Iowa, along with university collaborators showed that this inoculation method can cause the prion strains to change in a way that does not accurately reflect how the disease spreads naturally. They found that using a combination of peripheral inoculation (injection outside the brain) in natural hosts and using novel gene-targeted mice generated in a manner that provides a more natural expression of the inserted prion gene that gives a more accurate picture of how CWD behaves in the real world. The novel mouse model provides an important strategy to precisely assess the zoonotic potential (likelihood of transmission from animals to humans) of CWD and other animal prion diseases using natural routes of transmission. This will impact the tools used and direction of future studies of CWD and other prion diseases allowing more rapid and comprehensive responses to emerging questions aiding both the researchers at the producers they support…end
https://www.ars.usda.gov/research/project/?accnNo=440677&fy=202
***Moreover, sporadic disease has never been observed in breeding colonies or primate research laboratories, most notably among hundreds of animals over several decades of study at the National Institutes of Health25, and in nearly twenty older animals continuously housed in our own facility.***
Even if the prevailing view is that sporadic CJD is due to the spontaneous formation of CJD prions, it remains possible that its apparent sporadic nature may, at least in part, result from our limited capacity to identify an environmental origin.
https://www.nature.com/articles/srep11573
O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations
Emmanuel Comoy, Jacqueline Mikol, Valerie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France
Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases).
Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods.
*** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period,
***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold long incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014),
***is the third potentially zoonotic PD (with BSE and L-type BSE),
***thus questioning the origin of human sporadic cases.
We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.
===============
***thus questioning the origin of human sporadic cases***
===============
***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.
==============
https://prion2015.wordpress.com/wp-content/uploads/2015/05/prion2015abstracts.pdf
***Transmission data also revealed that several scrapie prions propagate in HuPrP-Tg mice with efficiency comparable to that of cattle BSE. While the efficiency of transmission at primary passage was low, subsequent passages resulted in a highly virulent prion disease in both Met129 and Val129 mice.
***Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
***These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
PRION 2016 TOKYO
Saturday, April 23, 2016
SCRAPIE WS-01: Prion diseases in animals and zoonotic potential 2016
Prion. 10:S15-S21. 2016 ISSN: 1933-6896 printl 1933-690X online
Taylor & Francis
Prion 2016 Animal Prion Disease Workshop Abstracts
WS-01: Prion diseases in animals and zoonotic potential
Transmission of the different scrapie isolates in these mice leads to the emergence of prion strain phenotypes that showed similar characteristics to those displayed by MM1 or VV2 sCJD prion.
These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
http://www.tandfonline.com/doi/abs/10.1080/19336896.2016.1163048?journalCode=kprn20
Title: Transmission of scrapie prions to primate after an extended silent incubation period)
*** In complement to the recent demonstration that humanized mice are susceptible to scrapie, we report here the first observation of direct transmission of a natural classical scrapie isolate to a macaque after a 10-year incubation period. Neuropathologic examination revealed all of the features of a prion disease: spongiform change, neuronal loss, and accumulation of PrPres throughout the CNS.
*** This observation strengthens the questioning of the harmlessness of scrapie to humans, at a time when protective measures for human and animal health are being dismantled and reduced as c-BSE is considered controlled and being eradicated.
*** Our results underscore the importance of precautionary and protective measures and the necessity for long-term experimental transmission studies to assess the zoonotic potential of other animal prion strains.
http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=313160
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Scrapie and CJD, Suspect Symptoms, Like Lambs To the Slaughter, a review 2022
2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284.
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt– Jakob disease: Implications for human health
Corinne Ida Lasmézas, Jean-Guy Fournier, Virginie Nouvel, +8, and Jean-Philippe DeslysAuthors Info & Affiliations
March 20, 2001
98 (7) 4142-4147
https://doi.org/10.1073/pnas.041490898
Abstract
There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt–Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.
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Discussion
One aim of this study was to determine the risk of secondary transmission to humans of vCJD, which is caused not by a primarily human strain of TSE agent but by the BSE strain having passed the species barrier to humans. This risk is tightly linked to the capacity of the BSE agent to adapt to primates and harbor enhanced virulence (i.e., induce disease after a short incubation period and provoke disease even if highly diluted) and to its pathogenicity after inoculation by the peripheral route. With respect to the latter, there are huge variations between different TSE agent strains and hosts. For example, the BSE agent is pathogenic to pigs after i.c. inoculation but not after oral administration (23). Thus, we wanted to know to what extent the BSE/vCJD agent is pathogenic to humans by the i.c. and i.v. routes. To achieve this, we used the macaque model. To monitor the evolution of the BSE agent in primates, but also to verify the identity of French vCJD, we conducted parallel transmission to C57BL/6 mice, allowing strain-typing. The experimental scheme is depicted in Fig. 1.
Characterization of the BSE Agent in Primates.
The identity of the lesion profiles obtained from the brains of the French patient with vCJD, two British patients with vCJD, and nonhuman primates infected with BSE provides experimental demonstration of the fact that the BSE agent strain has been transmitted to humans both in the U.K. and in France. Further, it lends support to the validity of the macaque model as a powerful tool for the study of vCJD. As far as the evolution of the BSE agent in primates is concerned, we observed an interesting phenomenon: at first passage of BSE in macaques and with vCJD, there was a polymorphism of the lesion profile in mice in the hippocampal region, with about half of them harboring much more severe vacuolation than the mice inoculated with cattle BSE. At second passage, the polymorphism tended to disappear, with all mice showing higher vacuolation scores in the hippocampus than cattle BSE mice. This observation suggests the appearance of a variant of the BSE agent at first passage in primates and its clonal selection during second passage in primates. The lesion profiles showed that it was still the BSE agent, but the progressive appearance of a “hippocampal signature” hallmarked the evolution toward a variant by essence more virulent to primates.
Characterization of the CJD and Scrapie Strains.
Controls were set up by transmitting one French and one U.S. scrapie isolate from ruminants as well as French sCJD and iCJD cases from humans. None of these revealed a lesion profile or transmission characteristics similar or close to those of BSE or vCJD, respectively, thus extending to the present French scrapie isolate the previous observation that the BSE agent was different from all known natural scrapie strains (4, 24).
The lesion profiles of sCJD and iCJD differed only slightly in severity of the lesions, but not in shape of the profile, revealing the identity of the causative agents. One of us reported the absence of similarity between sCJD (six cases) and U.K. scrapie (eight cases) in transmission characteristics in mice (4). Herein, we made the striking observation that the French natural scrapie strain (but not the U.S. scrapie strain) has the same lesion profile and transmission times in C57BL/6 mice as do the two human TSE strains studied. This strain “affiliation” was confirmed biochemically. There is no epidemiological evidence for a link between sheep scrapie and the occurrence of CJD in humans (25). However, such a link, if it is not a general rule, would be extremely difficult to establish because of the very low incidence of CJD as well as the existence of different isolates in humans and multiple strains in scrapie. Moreover, scrapie is transmissible to nonhuman primates (26). Thus, there is still a possibility that in some instances TSE strains infecting humans do share a common origin with scrapie, as pointed out by our findings.
Transmission of vCJD and BSE to Nonhuman Primates.
vCJD transmitted readily to the cynomolgus macaque after 2 years of incubation, which was comparable to the transmission obtained from first-passaged macaque BSE and much shorter than the interspecies transmission of BSE. Starting with 100 mg of BSE–macaque brain material, dilutions up to 4 μg still provoked disease. These data suggest that the BSE agent rapidly adapts to primates accompanied by enhanced virulence.
Examination of macaque brain inoculated with vCJD revealed a similar pathology to that with second-passage BSE. The distribution of vacuolation and gliosis, as well as the pattern of PrP deposition, including the dense, sometimes florid plaques, were similar to the human vCJD and the BSE hallmarks of the first passage (1, 2). These data show that the phenotype of BSE in primates is conserved over two passages. Moreover, they confirm that the BSE agent behaves similarly in humans and macaques, a precious finding that will prove useful in the near future for the design of pathogenesis or therapeutic studies. Because of the number of macaques examined in this study, we can now reliably state that the pathology, in particular the PrP deposition pattern provoked by BSE, is similar in older and very young animals. However, plaque deposition is greater, and mature florid plaques were more numerous, in the young, which may be correlated with a longer duration of the clinical phase observed in this animal (2). This is important with regard to the fact that vCJD has been diagnosed mainly in teenagers and young adults, which raises the concern that older patients may have been misdiagnosed because of an alternative phenotype of the disease.
One should bear in mind, however, that cynomolgus macaques are all homozygotes for methionine at codon 129 of the PrP gene. Thus, our observations may not be relevant to humans carrying one or both valine alleles; however, all patients with vCJD reported to date have been M/M at this position (27). Intravenous Transmissions to Nonhuman Primates.
Brain pathology was identical in macaques inoculated i.c. and i.v. The i.v. route proved to be very efficient for the transmission of BSE, as shown by the 2-year survival of the animals, which is only 5 months longer than that obtained after inoculating the same amount of agent i.c. As the i.v. injection of the infectious agent implies per se a delayed neuroinvasion compared with a direct inoculation in the brain, this slight lengthening of the incubation period cannot, at this stage, be interpreted as a lower efficiency of infection as regards the i.c. route. These data should be taken into account in the risk assessment of iatrogenic vCJD transmission by i.v. administration of biological products of human origin. They also constitute an incentive for a complete i.v. titration.
Conclusions
From BSE and vCJD transmissions in nonhuman primates, a number of conclusions can be drawn that are of major importance for human health: (i) human-adapted BSE appears to be a variant of the BSE agent that is more virulent for humans than cattle BSE and is efficiently transmitted by the peripheral route; (ii) the detection of vCJD in unusually young patients is probably not because of a lack of diagnosis of cases in older patients, thus raising the question of the source of human contamination with BSE early in life; and (iii) iatrogenic transmissions from patients with vCJD would be readily recognized by using the same diagnostic criteria as those applied to vCJD [clinical and pathological criteria (27) comprising neuronal loss and gliosis in the thalamus correlated with high MRI signal (28, 29)], whether such contaminations had occurred by the central or i.v. route. Primary and iatrogenic cases of vCJD could be distinguished on the basis of the patient's clinical history.
The risk assessment of biological products of human origin, notably those derived from blood, has been deeply modified by the appearance of vCJD. We confirm that the BSE agent has contaminated humans not only in the U.K. and the Republic of Ireland but also in France, and we show that its pathogenic properties for primates are being enhanced by a primary passage in humans. Considering the flow of potentially contaminated bovine-derived products between 1980 and 1996, it is obvious that further vCJD cases may occur outside the U.K. Thus, and in the light of the present study, it is necessary to sustain worldwide CJD surveillance regardless of national BSE incidence and to take all precautionary measures to avoid iatrogenic transmissions from vCJD.
www.pnas.org/doi/10.1073/pnas.041490898
Eur J Epidemiol. 2023; 38(7): 757–764. Published online 2023 May 16. doi: 10.1007/s10654-023-01004-5 PMCID: PMC10276107PMID: 37191829
Received: 31 January 2023 / Accepted: 6 April 2023 / Published online: 16 May 2023 © The Author(s) 2023
The role of environmental factors on sporadic Creutzfeldt-Jakob disease mortality: evidence from an age-period-cohort analysis
Angéline Denouel1
· Jean-Philippe Brandel1,2
· Danielle Seilhean1 · Jean-Louis Laplanche3,4
· Alexis Elbaz5
· Stéphane Haik1,2
Abstract
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of prion diseases. The causes of sCJD are still unknown and exogenous factors may play a role. Worldwide, the number of patients with sCJD has progressively increased over time. This increase can be partly explained by increasing life expectancy and better case ascertainment, but a true increase in the number of sCJD cases cannot be excluded. We estimated mortality rates from sCJD in France (1992–2016) and studied variation in mortality rates by age, period, and time.
We included all cases aged 45–89 years old who died with a probable/definite sCJD diagnosis based on the French national surveillance network. We used age-period-cohort (APC) Poisson regression models to study variation in mortality rates by sex, age, period, and time.
A total of 2475 sCJD cases aged 45–89 years were included. Mortality rates increased with age, reached a peak between 75 and 79 years, and decreased thereafter. Mortality rates were higher in women than men at younger ages and lower at older ages. The full APC model with a sex×age interaction provided the best fit to the data, thus in favour of sex, age, period, and cohort effects on mortality rates. In particular, mortality rates increased progressively with successive birth cohorts.
Based on 25 years of active surveillance in France, we show evidence for sex, age, period, and cohort effects on sCJD mortality. The identification of cohort effects suggests that environmental exposures may play a role in sCJD etiology.
Keywords Age-period-cohort model · Prion · Temporal trend · Sporadic Creutzfeldt-Jakob disease
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Worldwide, the number of patients with sCJD appears to have progressively increased over time [13]. This increase can be partly explained by increasing life expectancy as well as by better case ascertainment due to improved diagnostic tests and awareness of the disease among clinicians. Indeed, a relationship between surveillance intensity and sCJD incidence has been shown [14]. It cannot be excluded, however, that an actual increase of sCJD cases has occurred, and this hypothesis can be examined using age-period-cohort (APC) models.
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In this paper, we estimated mortality rates from sCJD in France over a 25-year period (1992–2016) based on data from the French national surveillance network.
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The overall sCJD mortality rate was 4.58 per 1,000,000 person-years (95% CI=4.39–4.78) (Table S1).
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Besides risk factors explored in case-control studies, the possibility of zoonotic risk factors remains a possibility that could account for an exogenous origin in some sCJD cases. Research on atypical forms of BSE (L-BSE, H-BSE) has revealed molecular similarities between the L-BSE strain and molecular subtypes of human sCJD, in particular the MV2 subtype [39]. Furthermore, L-BSE has been experimentally transmitted to non-human primates as efficiently as classical BSE responsible for vCJD in humans, and could be even more virulent [40–42]. The zoonotic risk associated with natural sheep scrapie has also been recently updated with the demonstration of an intracerebral transmission of scrapie to mice expressing the human prion protein during serial passages, as well as transmission of scrapie to primates. These observations highlight the possibility of a causal link between exposure to sheep scrapie and sCJD in some cases [43, 44]. A large increase in animal product consumption and the generalization of mechanically separated meat in developed countries over the last century may have contribute to increase the zoonotic prion pressure [45]. It would be of interest to observe the effect of safety measures implemented since the “mad cow crisis” to avoid population prion exposure on sCJD mortality in the next decades.
https://link.springer.com/article/10.1007/s10654-023-01004-5
“The zoonotic risk associated with natural sheep scrapie has also been recently updated with the demonstration of an intracerebral transmission of scrapie to mice expressing the human prion protein during serial passages, as well as transmission of scrapie to primates. These observations highlight the possibility of a causal link between exposure to sheep scrapie and sCJD in some cases [43, 44]. A large increase in animal product consumption and the generalization of mechanically separated meat in developed countries over the last century may have contribute to increase the zoonotic prion pressure [45]. It would be of interest to observe the effect of safety measures implemented since the “mad cow crisis” to avoid population prion exposure on sCJD mortality in the next decades.”
terry
***> CWD Action Plan National Program 103 Animal Health 2022-2027 UPDATE JANUARY 2026
https://prpsc.proboards.com/thread/189/action-national-program-animal-health
https://chronic-wasting-disease.blogspot.com/2026/01/cwd-action-plan-national-program-103.html
***> SCRAPIE TSE Prion USA RAPID RESPONSE URGENT UPDATES DECEMBER 25, 2025
***> CWD vs Scrapie Urgent Update
https://scrapie-usa.blogspot.com/2025/12/scrapie-tse-prion-usa-rapid-response.html
https://prpsc.proboards.com/thread/186/scrapie-prion-response-urgent-updates
***> 2026 USDA EXPLANATORY NOTES, APHIS, CWD, BSE, Scrapie, TSE, Prion
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/2026-usda-explanatory-notes-aphis-cwd.html
Research Project: Elucidating the Pathobiology and Transmission of Transmissible Spongiform Encephalopathies
Location: Virus and Prion Research
2025 Annual Report
https://transmissiblespongiformencephalopathy.blogspot.com/2025/12/ars-research-elucidating-pathobiology.html
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025 and history there from
https://www.researchgate.net/publication/396084947_USDA_National_Scrapie_Program_History_and_Bovine_Spongiform_Encephalopathy_BSE_TSE0AUpdate_2025
APHIS USDA Captive CWD Herds Update by State December 2025 Update
https://chronic-wasting-disease.blogspot.com/2025/12/aphis-usda-captive-cwd-herds-update-by.html
https://prpsc.proboards.com/thread/187/aphis-captive-herds-update-december
TUESDAY, SEPTEMBER 30, 2025
USDA EXPLANATORY NOTES ANIMAL AND PLANT HEALTH INSPECTION SERVICE 2025-2014 CHRONIC WASTING DISEASE CWD TSE CERVID
https://chronic-wasting-disease.blogspot.com/2025/09/usda-explanatory-notes-animal-and-plant.html
TUESDAY, SEPTEMBER 30, 2025
USDA National Scrapie Program History and Bovine Spongiform Encephalopathy BSE TSE Update 2025
https://bovineprp.blogspot.com/2025/09/usda-national-scrapie-program-history.html
THURSDAY, JANUARY 08, 2026
Confucius Ponders, what about Wild Pigs (Sus scrofa) and CWD TSE Prion, and the Environment, what if?
Confucius Ponders, what about Wild Pigs (Sus scrofa), they can cover some distance rather quickly, what about Wild Pigs (Sus scrofa) digging up the terrain, and as they do it, what if these Wild Pigs (Sus scrofa) were exposed to CWD TSE Prion, and then they go on exposing and saturating the land with CWD TSE Prion, then the soil becomes contaminated with CWD TSE Prion, then what about the plants that grow from that soil for the decades to come, what if???
https://prpsc.proboards.com/thread/190/confucius-ponders-wild-pigs-scrofa
https://chronic-wasting-disease.blogspot.com/2026/01/confucius-ponders-what-about-wild-pigs.html
WEDNESDAY, OCTOBER 15, 2025
US NATIONAL PRION DISEASE PATHOLOGY SURVEILLANCE CENTER CJD TSE REPORT 2025
https://prionunitusaupdate.blogspot.com/2025/10/us-national-prion-disease-pathology.html
FRIDAY, NOVEMBER 21, 2025
While no one was watching: Tenuous status of CDC prion unit, risk of CWD to people worry scientists
https://chronic-wasting-disease.blogspot.com/2025/11/while-no-one-was-watching-tenuous.html
SATURDAY, JANUARY 10, 2026
Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease, a review
https://creutzfeldt-jakob-disease.blogspot.com/2026/01/neuropsychiatric-symptoms-in-sporadic.html
https://prpsc.proboards.com/thread/191/neuropsychiatric-symptoms-sporadic-cjd-review
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
February 14, 2001
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr
Author Affiliations
JAMA. 2001;285(6):733-734. doi:10-1001/pubs.JAMA-ISSN-0098-7484-285-6-jlt0214
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
