PRNP and Gerstmann-Straussler-Scheinker syndrome: Pioneering studies in Gerstmann-Sträussler-Scheinker disease (GSS), familial human prion diseases associated with different PrP mutations, showed that purified amyloid preparations and PrPres aggregates obtained by in vitro proteolysis contained atypical 7–8 kDa PrP fragments, with ragged N and C termini [21]–[27], which were mainly composed of mutant PrP alleles [21], [25], [28]–[30].