APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.

ABSTRACT: Excess lipid droplet (LD) accumulation is implicated in various diseases, including Alzheimer's disease (AD), yet the mechanisms underlying this accumulation remain unclear. Apolipoprotein E (ApoE) is a droplet-associated protein, and its E4 variant confers the greatest genetic risk for late-onset AD while also being linked to increased neuroinflammation and LD accumulation. In this study, we compared the lipid and protein composition of hepatic LDs in targeted replacement mice expressing human E3 (neutral) or E4 (risk variant), under both baseline conditions and following lipopolysaccharide (LPS) administration. Lipidomic analysis revealed that E4 LDs exhibit a shift in glycerophospholipid distribution, with an increase in phosphatidylcholine species, such that their baseline profile rese

SUBMITTER: Friday CM 

PROVIDER: S-EPMC12187248 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature