Analysis of early effects of human APOE isoforms on Alzheimer's disease and type III hyperlipoproteinemia pathways using knock-in rat models with humanized APP and APOE.

ABSTRACT: APOE is a major genetic factor in late-onset Alzheimer's disease (LOAD), with APOE4 increasing risk, APOE3 acting as neutral, and APOE2 offering protection. APOE also plays key role in lipid metabolism, affecting both peripheral and central systems, particularly in lipoprotein metabolism in triglyceride and cholesterol regulation. APOE2 is linked to Hyperlipoproteinemia type III (HLP), characterized by mixed hypercholesterolemia and hypertriglyceridemia due to impaired binding to Low-Density Lipoproteins receptors. To explore the impact of human APOE isoforms on LOAD and lipid metabolism, we developed Long-Evans rats with human APOE2, APOE3, or APOE4 in place of rat Apoe. These rats were crossed with those carrying a humanized App allele to express human Aβ, which is more aggregation-prone

SUBMITTER: Yesiltepe M 

PROVIDER: S-EPMC11438110 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature