Longevity & AgingBlocking Fat Storage Enzyme Quiets Alzheimer's-Linked Brain Immune Cells
NIH scientists discovered that microglia — the brain's immune cells — require triglyceride-rich lipid droplet formation to mount inflammatory responses. Using human iPSC-derived microglia and APOE4 humanized mice, they showed that both bacterial (LPS) stimulation and the Alzheimer's risk genotype APOE4 trigger neutral lipid accumulation. Blocking the rate-limiting triglyceride synthesis enzymes DGAT1 and DGAT2 suppressed inflammatory cytokine release, altered phagocytosis, and reversed APOE4-associated disease transcriptional states. Critically, DGAT inhibition also rescued microglial surveillance defects in living mouse brain slices carrying the APOE4 gene, pointing to triglyceride metabolism as a druggable node for neuroinflammation in Alzheimer's disease.
