Cholesterol-lowering drugs reduce APP processing to Aβ by inducing APP dimerization.

ABSTRACT: Amyloid beta (Aβ) is a major component of amyloid plaques, which are a key pathological hallmark found in the brains of Alzheimer's disease (AD) patients. We show that statins are effective at reducing Aβ in human neurons from nondemented control subjects, as well as subjects with familial AD and sporadic AD. Aβ is derived from amyloid precursor protein (APP) through sequential proteolytic cleavage by BACE1 and γ-secretase. While previous studies have shown that cholesterol metabolism regulates APP processing to Aβ, the mechanism is not well understood. We used iPSC-derived neurons and bimolecular fluorescence complementation assays in transfected cells to elucidate how altering cholesterol metabolism influences APP processing. Altering cholesterol metabolism using statins decreased the ge

SUBMITTER: Langness VF 

PROVIDER: S-EPMC8098827 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature