Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis.

ABSTRACT: Cholesterol dyshomeostasis has been linked to the pathogenesis of sporadic Alzheimer's disease (AD). In furthering the understanding of mechanisms by which increased levels of circulating cholesterol augments the risk of developing sporadic AD, others and we have reported that low-density lipoprotein (LDL) enters brain parenchyma by disrupting the blood-brain barrier and that endolysosome de-acidification plays a role in LDL-induced amyloidogenesis in neurons. Here, we tested the hypothesis that endolysosome de-acidification was central to amyloid-β (Aβ) generation and that acidifying endolysosomes protects against LDL-induced increases in Aβ levels in neurons. We demonstrated that LDL, but not HDL, de-acidified endolysosomes and increased intraneuronal and secreted levels of Aβ. ML-SA1, a

SUBMITTER: Hui L 

PROVIDER: S-EPMC6425476 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature