Whereas biochemical techniques allowing direct investigation of PrPSc conformation are lacking, the issue of deriving conformational properties of PrPSc aggregates by indirect approaches, such as the study of PrPres fragments by immunoblotting, was made even more challenging by i) the need to compare PrPSc from different species which have different PrP primary structures, and ii) the presence of conspicuous amounts of partially protease sensitive PrPSc in the prion diseases under investigation, whose labile nature undermines the use of protease-based techniques. Here, PRNP is linked to prion disease.