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. 2022 Sep 15;10:999024. doi: 10.3389/fcell.2022.999024

FIGURE 2.

FIGURE 2

Microglia with different phenotypes participate in AD related pathological activities. Depending on the stimulation of AD microenvironment, resting microglia can be transformed into M1 phenotype microglia with neurotoxicity or M2 phenotype. microglia with neuroprotection. Under the influence of amyloid beta (Aβ) plaques, activated M1 microglia overproduce proinflammatory cytokines (IL-1β, IL-6, and TNF-α), which have toxic effects on neurons. M2 microglia are involved in modulating the release of anti-inflammatory mediators (TGF-β, IL-4, and IL-10), thereby reducing inflammation. Moreover, M2 microglia also cleared Aβ peptides by phagocytosis, limiting the damage of Aβ peptides to the adjacent neuropil to the greatest extent. Microglia could indirectly affect neuronal activity through astrocytes. Finally, scRNA-seq results indicated multiple activation states in microglia are context-dependent in response to Aβ accumulation, including disease-associated microglia (DAM) localized in the vicinity of the Aβ plaques, Cyc proliferating microglia, IFN-I microglia, and MHC-II population.