Fig. 1
From: Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis
A self-sustaining feedback loop of neuroinflammation mediated by the interplay between T cells and microglia. Neurotoxic protein (Aβ and tau) accumulation in AD triggers microglial activation, initiating a cascade of pathological events. Activated microglia release chemokines that recruit T cells to the brain parenchyma, where T cells secrete cytotoxic factors that exacerbate Aβ production and aggregation. This further amplifies microglial activation, leading to the assembly of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. This critical multi-protein complex activates caspase-1, driving the release of pro-inflammatory cytokines, including IL-1β and IL-18. The resulting self-sustaining cycle intensifies T-cell infiltration and neuroinflammation, ultimately accelerating neurodegeneration.