Full-length amyloid precursor protein regulates lipoprotein metabolism and amyloid-β clearance in human astrocytes.

ABSTRACT: Mounting evidence suggests that alterations in cholesterol homeostasis are involved in Alzheimer's disease (AD) pathogenesis. Amyloid precursor protein (APP) or multiple fragments generated by proteolytic processing of APP have previously been implicated in the regulation of cholesterol metabolism. However, the physiological function of APP in regulating lipoprotein homeostasis in astrocytes, which are responsible for de novo cholesterol biosynthesis and regulation in the brain, remains unclear. To address this, here we used CRISPR/Cas9 genome editing to generate isogenic APP-knockout (KO) human induced pluripotent stem cells (hiPSCs) and differentiated them into human astrocytes. We found that APP-KO astrocytes have reduced cholesterol and elevated levels of sterol regulatory eleme

SUBMITTER: Fong LK 

PROVIDER: S-EPMC6065173 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature