NR AOTV
AU Head,M.W.; Bunn,T.J.R.; Bishop,M.T.; Knight,R.S.G.; Will,R.G.; Ironside,J.W.
TI Heterogeneity in the abnormal prion protein isoforms found in the brains of sporadic but not variant Creutzfeldt-Jakob disease patients
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - DG-03
PT Konferenz-Poster
AB Human prion diseases can occur as an idiopathic disorder (termed sporadic Creutzfeldt-Jakob disease, sCJD) or can be acquired, as is the case for variant Creutzfeldt-Jakob disease (vCJD). These disorders are characterised by the accumulation of an abnormal form of the host-encoded prion protein termed PrPsc in the brains of affected individuals. PrPsc has been proposed to be the principal, if not sole component of the infectious agent, and its accumulation in the brain the primary event leading to neurodegeneration. A major question remains whether self-propagating structural differences in PrPsc might account for the clinico-pathological diversity evident in CJD and whether prion protein isotypes underlie the existence of strains of causative agent. Here we report the results of a large-scale biochemical and genetic study of protease-resistant prion protein, PrPres, from autopsy-proven cases of vCJD and compare these with cases of sCJD disease in the UK over the period 1991-2002. The results show PrPres in vCJD to be remarkably stereotyped, occurring exclusively in a 19kDa form (type 2) characterized by high N-linked glycosylation site occupancy and encoding methionine at position 129. In contrast considerable heterogeneity in PrPres exists both between and within cases of sCJD. PrPres in sCJD occurs as either a 21kDa form (type 1) or a 19kDa form (type 2) and can contain either methionine or valine at position 129. A significant minority of sCJD cases show both type 1 and type 2 PrPres. However vCJD and sCJD could be distinguished between on the basis of PrPres glycoform ratio. The close correlation of sCJD subtype frequency found in this UK study with the results of a previous study of a European and North American cohort argues against the existence of BSE-related CJD with a sporadic CJD-like phenotype occurring in the UK.
AD M.W.Head, T.J.R.Bunn, M.Bishop, R.Knight, R.G.Will, J.W.Ironside, National CJD Surveillance Unit, University of Edinburgh, UK
SP englisch
PO Deutschland