Linking APOE4/4 genotype to microglial lipid droplets and neurotoxicity in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that primarily affects the elderly population worldwide. The accumulation of lipids within cells surrounding amyloid plaques is a principal neuropathological feature of AD. The APOE ε4 allele has been identified as the strongest genetic risk factor for AD. Recent studies have shown that lipid metabolism dysregulation, manifested as the accumulation of lipid droplets (LDs), occurs in a subset of microglia known as lipid-droplet-accumulating microglia (LDAM). These cells may play a crucial role in aging and the development of neurodegenerative diseases. A recent study highlights the role of microglial LD accumulation in AD pathology, specifically focusing on the role of ACSL1 in LD formation and neurotoxicity in microglia. The study also suggests that LD accumulation, inflammation, and tau uptake may have a synergistic effect. The APOE4/4 genotype causes a lipid metabolic imbalance and has an impact on the development of AD. These insights may pave the way for targeted therapies against LD accumulation in microglia during the progression of AD. [Extracted from the article]