Typing prion isoforms

The central event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrP super(C)) into the pathological and protease-resistant isoform (PrP super(res)). The conversion produces PrP super(res) types with distinct physical and chemical characteristics, which may represent the molecular basis for prion strains. Collinge et al. extended our original observation of two types of PrP super(res) in sporadic Creutzfeldt-Jakob disease (sCJD), into iatrogenic CJD (iCJD) and the so-called new variant CJD (vCJD), which may have been acquired from bovine spongiform encephalopathy (BSE). On the basis of electrophoretic mobilities and ratios of differently glycosylated isoforms, Collinge et al. reported a total of four types of PrP super(res), but our analysis of a large series of additional cases including kuru (associated with cannibalism in the Fore tribe of New Guinea), iCJD and vCJD reveals only two patterns of electrophoretic mobility as we originally reported.