The concept of cell-free aggregation assays stems from the discovery of the protein-only mechanism for the propagation of the prion protein (PrP) as the sole pathogenic agent of transmissible spongiform encephalopathies including CJD and other human and animal prion diseases, such as scrapie in sheep, and chronic wasting disease in cervids [68, 69]. Here, PRNP is linked to Creutzfeldt Jacob disease.