The age-related microglial transformation in Alzheimer's disease pathogenesis.

Neuroinflammatory responses mediated by microglia, the resident immune cells of the central nervous system, have long been a subject of study in the field of Alzheimer's disease (AD). Microglia express a wide range of receptors that act as molecular sensors, through which they can fulfill their various functions. In this review, we first analyzed the changes in the expression levels of microglial membrane receptors SR-A, TREM2, CD36, CD33, and CR3 in aging and AD and described the different roles of these receptors in amyloid-beta clearance and inflammatory responses. Two classical hallmarks of AD are extracellular amyloid-beta deposits and intracellular aggregated phosphorylated tau. In AD, microglia reaction was initially thought to be triggered by amyloid deposits. New evidence showed it also associated with increased phosphorylation of tau. However, which first appeared and induced activated microglia is not clear. Then we summarized diverse opinions on it. Besides, as AD is tightly linked to aging, and microglia changes dramatically on aging, yet the relative impacts of both aging and microglia are less frequently considered, so at last, we discussed the roles of aging microglia in AD. We hope to provide a reference for subsequent research.
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