Microglia

Microglia are the brain's resident innate immune cells, derived from yolk-sac progenitors that colonise the CNS during early embryogenesis and are maintained independently of peripheral monocytes. In their homeostatic state they continuously survey the parenchyma with ramified processes, pruning synapses, clearing apoptotic debris and releasing neurotrophic factors. With age, microglia shift toward a 'primed' or dystrophic state characterised by altered morphology, impaired phagocytosis and heightened inflammatory reactivity to secondary stimuli, contributing to neuroinflammation. In Alzheimer's disease, GWAS hits in genes such as TREM2, CR1 and BIN1 strongly implicate microglial dysfunction in pathogenesis, positioning microglia as both sensors of amyloid and tau pathology and as active modulators of disease progression.