Disease-associated prion protein (PrP) can be distinguished from the cellular isoform (PrP) by conformation-dependent immunoassay (CDI). This technique exploits the presence of an epitope, accessible in PrP, but only unmasked by denaturation in PrP. In this study, we investigated PrP in different brain regions in variant and sporadic Creutzfeldt–Jakob disease (CJD) by using CDI, and directly compared the results with those obtained using the more commonly employed protease digestion and Western blotting. In general, there was good agreement between the results, although there were certain discrepancies in relative abundance when the regional distribution in variant CJD cases was considered. The results largely confirmed the previously described targeting of different brain regions by variant and sporadic CJD. Additionally, the combination of protease digestion and CDI detection demonstrated, for the first time, the presence of PrP in variant CJD brains that is susceptible to proteolysis under standard conditions.


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