NR AXMB
AU Faucheux,B.A.; Privat,N.; Sazdovitch,V.; Brandel,J.P.; Matos,A.; Maurage,C.A.; Laplanche,J.L.; Deslys,J.P.; Hauw,J.J.; Haik,S.
TI Neuronal Loss and Prion Protein (PrP) Depositon in Sporadic Creutzfeldt-Jakob Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.07
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB The mechanisms involved in neurodegeneration are still poorly understood in human prion diseases, although neuronal death is a central component of the neuropathological pattern. Neurodegeneration varies according to the forms of the disease, brain regions and neuronal populations. PrPres toxicity has been proposed to play a central role in the degeneration of neurons in transmissible spongiform encephalopathies. Since neurons of the granule cell layer of the cerebellum are severely depleted in some cases of sporadic Creutzfeldt-Jakob disease, we investigated neuronal densities in this brain region and studied in parallel the accumulation of abnormal PrP. We quantified the density of these cells (estimated with a computer-assisted image analysis system) and markers of neuropathological lesions (spongiosis, gliosis) in a group of patients with sporadic Creutzfeldt-Jakob disease and a group of matched controls. We studied the location and patterns of the prion protein deposits using two different techniques (immuno-histochemistry of tissue sections; paraffin-embedded tissue blots). The biochemical characteristics of proteinase K resistant prion protein (PrPres) present in the cerebellum was determined by Western blotting of tissue homogenates. The polymorphism at codon 129 of the PRNP gene was deduced from DNA sequencing. Based on precise quantifications, our findings clearly demonstrate a strong and highly significant statistical correlation between neuronal loss and the amount of PrPres deposition in patients with sporadic Creutzfeldt-Jakob disease. These data support the hypothesis that abnormal PrP accumulation can compromise cell homeostasis and end in the degeneration of neurones. This work was carried out with the support of DRCD of AP-HP and INSERM.
AD B. Faucheux, N. Privat, V. Sazdovitch, J.P. Brandel, S. Haik, Salpetriere Hospital, INSERM France; A. Matos, J.J. Hauw, Salpetriere Hospital, Neuropathology Laboratory, France; C.A. Maurage, R Salengro Hospital, Cytological and Pathological Anatomy, France; J.L. Laplanche, Lariboisiere Hospital, Biochemistry-Molecular Biology, France; J.P. Deslys, Commissariat a l'Energie Atomique, SEPIA, DSV/IMETI, France
SP englisch
PO Schottland