Stabilization of intracellular trafficking and metabolism of amyloid ß-protein precursor and Alcadein ß by apolipoprotein E.

ABSTRACT

Intracellular metabolism of amyloid ß-protein precursor (APP) is important for the pathogenesis of Alzheimer's disease (AD). Alcadeins (Alcα, Alcß, and Alcγ) are neural membrane proteins similar to APP in their localization, metabolism, and cellular function. Isoform ε4 of apolipoprotein E (ApoE) is a major risk factor for AD. We found that ApoE expression attenuated intracellular trafficking of APP and Alcß, resulting in metabolic stabilization of both proteins. By contrast, Alcα intracellular proteolysis was facilitated by ApoE expression, which was not due to an increase in the primary cleavage of Alcα. This difference may result from binding of ApoE to membrane proteins.