Protective or Pathogenic? Microglial Responses at the Intersection of Amyloid-β, Tau, and Neuroinflammation in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, pathological tau aggregation, and neuronal loss. Neuroinflammation is increasingly recognized as a contributor to disease progression, with microglia playing a central and context-dependent role. This mini-review examines the reciprocal interactions between microglia and neuroinflammation in AD, focusing on Aβ handling, inflammatory signaling, and tau pathology. We discuss how microglia may support pathological protein clearance while also promoting inflammatory responses through pathways involving NF-κB, the NLRP3 inflammasome, and oxidative stress–TRPM2 signaling. We further explore how microglial processing of tau may either limit its accumulation or facilitate its propagation. These findings highlight the dual role of microglia in AD, functioning as both protective responders and potential drivers of neuroinflammation and neurodegeneration.