Alzheimer's disease (AD) is a severe degenerative neurological disease which leads to progressive cognitive decline and memory impairment. We have affirmed amyloid-β (Aβ) plaques and tau tangles as the primary pathological hallmarks for a long time. However, many therapeutic approaches have found out that both Aβ and tau alone have achieved little success. Increasing evidence indicates that the neuroinflammation, which primarily related with microglia and astrocytes, takes the central role of causing and exacerbating the disease. Microglia and astrocytes not only respond to Aβ and tau but also control their accumulation, propagation, and associated neurotoxicity. They are also influenced by a kind ofrisky gene related to late-onset AD calls ApoE, which can further modulate them by regulating lipid metabolism and glial responses. This review synthesizes current knowledge on the roles of microglia, astrocytes, Aβ, tau, and ApoE in AD, emphasizing their interconnected contributions to pathogenesis and therapeutic opportunities.