APOE genotype alters the lipid droplet proteome and modulates droplet dynamics

The microglial immune response is a significant contributor to Alzheimer’s disease (AD) pathophysiology and neurodegeneration. Aging microglia accumulate lipid droplets (LDs), have high levels of reactive oxygen species, secrete pro‐inflammatory cytokines, and are defective in phagocytosis. The E4 allele of Apolipoprotein E (APOE) is the strongest genetic risk factor for late‐onset AD, and is associated with heightened neuroinflammation and increased LD formation. We hypothesize E4 microglia have increased LD formation under basal conditions and a higher capacity to form LDs under stress, resulting in greater pro‐inflammatory cytokine production. We characterized LD development in microglia in the context of APOE genotype and analyzed LD surface proteins and lipid content from control and lipopolysaccharide (LPS) stimulated ApoE3 and ApoE4 mice.