Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease

Abstract

Background: Alzheimer’s disease (AD) and prion diseases such as sporadic Creutzfeldt-Jakob disease (sCJD) share common features concerning their molecular pathogenesis and neuropathological presentation and the coexistence of AD and CJD in patients suggest an association between the deposition of the proteolytically processed form of the amyloid precursor protein, β-amyloid (Aβ), which deposits in AD, and the abnormal form of the prion protein, PrP^Sc, which deposits in sCJD. Methods: We have characterized sCJD patients (n = 14), AD patients (n = 5) and nondemented controls (n = 5) with respect to the deposition of PrP^Sc and Aβ morphologically, biochemically and genetically and correlated these findings to clinical data. Results: sCJD-diseased individuals with abundant deposits of Aβ present with a specific clinicopathological profile, defined by higher age at disease onset, long disease duration, a genetic profile and only minimal amounts of PrP^Sc in the cerebellum. Conclusion: The co-occurrence of pathological changes typical for sCJD and AD in combination with the inverse association between accumulation of Aβ and PrP^Sc in a subgroup of sCJD patients is indicative of common pathways involved in the generation or clearance of Aβ and PrP^Sc in a subgroup of sCJD patients.