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Microglial Fat, Not Just Plaques, Emerges as Target in Alzheimer’s

Researchers trace DGAT2 buildup that diverts fatty acids into storage to reveal a metabolic treatment path.

Overview

  • An Immunity study from Purdue with Cleveland Clinic links amyloid‑beta plaques to lipid‑loaded microglia that underperform in clearing debris.
  • In human Alzheimer’s tissue, microglia within 10 micrometers of plaques carried about twice the lipid droplets and cleared roughly 40% less amyloid beta.
  • The team identifies DGAT2 accumulation from impaired degradation as the switch that channels free fatty acids into triacylglycerol and droplet formation.
  • Targeting DGAT2 with an inhibitor or a degrader reduced brain fat, restored microglial plaque‑clearing activity, and improved neuronal‑health markers in animal models.
  • Lipid droplet burden rose with age and disease stage, supporting a glia‑focused lipid model that complements amyloid/tau views and points to preclinical therapeutic avenues backed by NIH and DoD funding.