Pioneering studies in GSS showed that purified amyloid preparations and the PrPres obtained by in vitro proteolysis mainly comprise atypical unglycosylated 7-8 kDa PrP fragments with ragged N and C termini, primarily composed of mutant PrP, which are lacking in classic TSEs such as CJD and FI (Figure 1) [102, 146–151]. This evidence concerns the gene PRNP and Creutzfeldt Jacob disease.