Two major determinants of the phenotypic heterogeneity of sCJD. (a) The PRNP genotype at polymorphic codon 129. (b) Type of PrPSc in the brain. Types 1 and 2 PrPSc are cleaved by proteinase K at different sites (at residues 82 and 97, respectively) . (c) In western blot analysis, types 1 and 2 PrPSc are distinguishable by the size of the proteinase K-resistant core of the unglycosylated PrPSc (21 and 19 kDa, respectively) .