Schematic presentation of the mechanism, illustrating genesis of PrPSc triggered by rPrP fibrils. In a first step, rPrP fibrils seeded atypical PrPres, a transmissible form of PrP that replicates silently without causing clinical disease. Replication of atypical PrPres occasionally produces PrPSc in seeding events that appears to be rare and stochastic as described for a deformed templating mechanism. PrPSc replicates faster than atypical PrPres and eventually replaces it during serial passages. The two forms atypical PrPres and PrPSc can be distinguished after PK treatment via staining Western blot analyses with discriminating antibodies. Atypical PrPres, alternative self-replicating state of prion protein; PrPSc, prion protein scrapie isoform; rPrP, recombinant prion protein. From [185].