Involvement of Dab1 in APP processing and β-amyloid deposition in sporadic Creutzfeldt–Jakob patients

Abstract

Alzheimer's disease and prion pathologies (e.g., Creutzfeldt–Jakob disease (CJD)) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. Dab1 has been implicated in the regulation of amyloid precursor protein (APP), but a direct link between human prion diseases and Dab1/APP interactions has not been published. Here we examined this putative relationship in 17 cases of sporadic CJD (sCJD) post-mortem. Biochemical analyses of brain tissue revealed two groups, which also correlated with PrP sc types 1 and 2. One group with PrP sc type 1 showed increased Dab1 phosphorylation and lower βCTF production with an absence of Aβ deposition. The second sCJD group, which carried PrP sc type 2, showed lower levels of Dab1 phosphorylation and βCTF production, and Aβ deposition. Thus, the present observations suggest a correlation between Dab1 phosphorylation, Aβ deposition and PrP sc type in sCJD.