High-Fat Diet-Induced Excessive Accumulation of Cerebral Cholesterol Esters and Microglial Dysfunction Exacerbate Alzheimer's Disease Pathology in APP^NL-G-F mice.

ABSTRACT: Epidemiological studies have identified high-fat diet (HFD)-induced obesity as a risk factor for Alzheimer's disease (AD), yet the underlying molecular mechanisms remain inadequately elucidated. Microglia, the brain's innate immune cells, are pivotal in AD brain by engulfing β-amyloid (Aβ) peptides and compacting poorly consolidated Aβ plaques. Microglia are highly susceptible to the metabolic milieu; however, it is unclear how long-term HFD alters the lipid environment and influences microglial phenotype in AD brains. In this study, APP^NL-G-F knock-in AD model mice were fed an HFD for 9-27 weeks and subsequently analyzed for Aβ pathology and microglial function. Our findings indicated that HFD intake accelerated Aβ deposition, attenuated the recruitment of microglia to the plaq

SUBMITTER: Yang S 

PROVIDER: S-EPMC12367945 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature