NR AXOE
AU Head,M.; Schiller,K.; Peden,A.; Yull,H.; Bishop,M.; Ironside,J.
TI Prion Protein Analysis in Familial Human Prion Diseases
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.130
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: The abnormal prion protein (PrPsc) found in the central nervous system (CNS) in sporadic CJD and variant CJD is characterised by a predominant proteaseresistant core fragment size of either ~21kDa (type 1) or ~19kDa (type 2). These types may be further sub-classified according to the ratio of the three glycoforms as either A, when the mono- or non-glycosylated forms are the most abundant, or B in cases where the diglycosylated form predominates. According to one reading of the prion hypothesis, differences in disease phenotype are contingent on the presence of one of these PrP types in conjunction with the host genotype at codon 129 of the prion protein gene.
Objective: We have sought to examine tissues from cases of human prion disease associated with mutations in the PRNP gene to determine if these too may be easily classified according to the system employed for sporadic and variant CJD.
Methods: We have performed Western blot analysis of the PrPsc types in the CNS of a cohort of cases of human prion disease associated with mutations in PRNP, including cases of familial CJD, Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia. We have also had the opportunity to examine peripheral tissue involvement in a case of Gerstmann-Sträussler-Scheinker disease.
Results: The results confirm that familial prion diseases exhibit a very broad range of possible PrPsc types: Some resemble those found in sporadic CJD, while others differ in fragment size, glycosylation ratio and protease sensitivity to those found in sporadic and variant CJD.
Conclusions: This implies that some mutations associated with familial human prion diseases affect prion protein metabolism in a manner that differs from the course of events that occur in sporadic and variant CJD.
AD M. Head, K. Schiller, A. Peden, H. Yull, M. Bishop, J. Ironside, University of Edinburgh, National CJD Surveillance Unit, UK
SP englisch
PO Schottland