Genetic Insights Reveal Microglial Changes and Lipid Droplet Accumulation in Alzheimer’s Risk
The study identifies a functional Alzheimer's disease risk variant in the PICALM gene that disrupts PU.1 binding, reduces PICALM expression in microglia, leading to increased lipid droplet accumulation, lysosomal dysfunction, and impaired phagocytosis, which may contribute to disease pathology.