Original histological phenotype after the experimental transmission to primate of an unusual human prionopathy (VPSPr)
Brain Pathol. 2023 Sep; 33(Suppl 1): e13194.
Published online 2023 Sep 6.
PMCID: PMC10483180
PMID: 37674376
Special Issue: Abstracts of the 20th International Congress of Neuropathology, Berlin, Germany, September 13–16, 2023
snip...
Original histological phenotype after the experimental transmission to primate of an unusual human prionopathy (VPSPr)
J. Mikol 1, J. Delmotte1, W. Zou2,3, J. P. Deslys1, E. Comoy1 1Commissariat à l'energie Atomique, Institut François Jacob/Prion research Group, Fontenay‐aux‐Roses, France; 2Case Western Reserve University School of Medicine, Department of Pathology, Cleveland, OH, United States; 3Institute of Neurology, Nanchang, China
VPSPr, a novel rare human prion disease described in 2010 is characterized by the accumulation of abnormal PrPd with a limited resistance to proteolysis. It showed uncertain infectivity in transgenic mouse models. Recent publications report VPSPr cases with different unevocative clinical pictures, leading the authors to consider that VPSPr might be underestimated. One of our macaques intracerebrally inoculated with a brain sample derived from a VPSPr patient (Met/Val at codon 129) exhibited after 8.5 years of silent incubation several episodes of self‐aggression first focused on his left leg, which extended to the whole hindquarters, and abnormalities of both hind limbs sensitive conduction. We performed euthanasia 4 months later for humane reasons and examined brain tissues with histological techniques. Pathological examination revealed a spongiform change decreasing from the frontal to the occipital cortex, also present in the thalamus, the basal ganglia, the hippocampus, mild brainstem and spinal cord, accompanied with a massive neuronal vacuolation and reactive astrocytosis. Purkinje cells were rarefied and vacuolated. Abnormal PrPd deposition was present as synaptic deposits mixed with some mini‐aggregates of PrPd diffused in the tissue or packed in small fussy unlimited area of variable intensity, appearing as pre‐plaques. These lesions, never previously observed in primates exposed to other prion strains, were mainly observed in the insula and the frontal cortex but were absent in the thalamus, the basal ganglia and the hippocampus. Furthermore, we observed massive Ab deposits, but not in the hippocampus except the subiculum, not co‐localized with PrPd. In contrast, a two‐times older animal had three‐times less deposits. The original disease phenotype observed in this primate will be discussed and compared to the expressions of VPSPr in humans, and other prion diseases in the macaque model. PS9‐ND‐A186
“Recent publications report VPSPr cases with different unevocative clinical pictures, leading the authors to consider that VPSPr might be underestimated. “
“One of our macaques intracerebrally inoculated with a brain sample derived from a VPSPr patient (Met/Val at codon 129) exhibited after 8.5 years of silent incubation several episodes of self‐aggression first focused on his left leg, which extended to the whole hindquarters, and abnormalities of both hind limbs sensitive conduction.”
Yup, as predicted…
CANADA
Definite and probable CJD, 1998-2023
As of November 30, 2023
Year Sporadic Iatrogenic Genetic vCJD Total
SNIP...
2023, STILL NO MENTION OF VPSPr TSE Prion in Canada statistics...terry
PLEASE NOTE, Canada does not mention VPSPr Variably protease-sensitive prionopathy and you can read why here ;
WHY do some countries count vpspr as sporadic cjd tse prion, and some countries don't?
THIS problem must be addressed immediately imo.
WE have the USA classifying Variably protease-sensitive prionopathy (VPSPr) (formerly known as Protease Sensitive Prionopathy) as sporadic Creutzfeldt Jakob Disease sCJD, and we have Canada not even mentioning in on there statistics links, like vpspr does not even exist, so this is a problem for any valid surveillance imo. IN fact, personal communication from Canada Surveillance et al;
QUOTE;
''Well Terry, we have the data. We simply do not report it separately because we do not believe it has any specific epidemiologic significance, including zoonotic transmission (this opinion is shared unanimously by the international CJD surveillance community, and was established very quickly after the discovery of VPSPr). The key reason in my mind why the US system reports it – in a footnote to their sporadic CJD data – is that they discovered it, and want to follow up on it publicly to validate the reality of their finding scientifically (which is distinct from its significance).''
''The simple answer to your question is that we do not track VPSPr separately, as we view is as a form of sporadic CJD with an unusual phenotype but no specific epidemiological significance. Even the USA surveillance figures do not report it separately.''
end
Hell of a way for a surveillance system for any country to look for any suspect unusual zoonosis zoonotic disease from any mutated TSE Prion strain from any species. ...terry
TUESDAY, DECEMBER 12, 2023
***> CREUTZFELDT JAKOB DISEASE TSE PRION DISEASE UPDATE USA DECEMBER 2023 <***
***> 2023 Professor John Collinge on tackling prion diseases <***
“The best-known human prion disease is sporadic Creutzfeldt-Jakob disease (sCJD), a rapidly progressive dementia which accounts for around 1 in 5000 deaths worldwide.”
There is accumulating evidence also for iatrogenic AD.
Understanding prion biology, and in particular how propagation of prions leads to neurodegeneration, is therefore of central research importance in medicine.
terry
