PRNP and prion disease: Subsequent studies, however, provided evidence that ADAM10-cleaved PrPSc was mostly associated with large perivascular and possibly inert plaques, whereas diffusible oligomeric or sub-fibrillar (and presumably more neurotoxic) PrPSc assemblies dominating in many prion diseases mostly result from the conversion of GPI-anchored PrP (Aguilar-Calvo et al. 2020; Callender et al. 2020; Sevillano et al. 2020).