In
prion diseases, genotypic classification has been useful to understand the
clinical course and pathological changes. However, among patients with the same
prion protein (PrP) genotype, there are variations in the pathological and clinical phenotype. Recently, PrP typing was proposed by the molecular weight of
protease-resistant PrP (PrPres). Combined with genotype and PrPres typing,
sporadic Creutzfeldt-Jakob disease (CJD) could be classified precisely. In addition, we found the fragmented PrP molecules to differentiate between dura-classic CJD and dura-plaque type CJD. We report herein that the fragmented PrP is a useful marker to classify human
prion diseases, and also a clue to analyze abnormal PrP structures. The fragmented PrP was detected in patients with classic-type CJD, sporadic thalamic-type CJD, familial CJD with
codon 200 or 232 mutation, or familial
Gerstmann-Straussler syndrome (GSS) with
codon 102 mutation. Among patients with type-1 abnormal PrP, the transmission study was successful in
sporadic CJD with type 1 PrPres and the fragment PrP, but not in CJD without the fragmented PrP. Thus, in the
prion field, type-specific PrP structure contributes to the clinicopathology and transmissibility.