A comparative study of abnormal prion protein isoforms between Gerstmann-Straussler-Scheinker syndrome and Creutzfeldt-Jakob disease

Proteinase K (PK)-resistant prion protein (PrP(res)) isoforms were examined in three patients with Gerstmann-Straussler-Scheinker syndrome (GSS) carrying proline-to-leucine mutation at codon 102 in prion protein gene (PRNP), and in nine patients with sporadic Creutzfeldt-Jakob disease (CJD). PrP(res) isoform termed 'type A', which showed a more prominent band of highly glycosylated form than both a lower glycosylated band and an unglycosylated band in immunoblotting, was exclusively found in the GSS patients examined. In eight of nine CJD patients, electrophoretic mobilities of three PrP(res) glycoforms were similar to type A, but the ratio of these glycoforms termed 'type B' was distinct from that of type A. On the other hand, one sporadic CJD case with wild-type PRNP had a different PrP(res) isoform termed type C, which showed higher molecular shift of each of the PrP(res) glycoforms. There was no significant relationships among genotypes, clinical features and PrP(res) isoforms in sporadic CJD cases. Our finding suggests that type A PrP(res) isoform is specifically found in the patients with GSS carrying codon 102 mutation, and there are at least two different PrP(res) isoforms in the patients with sporadic CJD.