Table 1.

The pathological and protective mechanisms of microglia involvement in AD.

Pathological events	Molecules/Genes	Impact on microglial function	References
Microglia and Aβ	SR-A	promote microglia adhesion to Aβ and increase microglia uptake of Aβ	Frenkel et al. (2013)
	CD36	play a dichotomous role in Aβ phagocytosis	Kim et al. (2017)
	RAGE	play a dichotomous role in Aβ phagocytosis	Deane et al. (2012)
	APOE	APOE ε4 genotype is related to a dampened microglial response to amyloid plaques	Nguyen et al. (2020)
	CR1	promote the phagocytosis of Aβ by microglia	Crehan et al. (2013)
	TREM2	play a dichotomous role in Aβ phagocytosis	Ulland et al. (2017)
	CD33	reduce the phagocytosis of Aβ by microglia	Yin et al. (2017)
	ABCA7	promote the phagocytosis of Aβ by microglia	Aikawa et al. (2019)
Microglia and Neuroinflammation	NLRP3	aggravate microglia-mediated inflammatory response	Heneka et al. (2013)
	SOCS	play a protective role by balancing the inflammatory response	Ruganzu et al. (2021)
	CX3CR1	CX3CR1 deficiency aggravates tau phosphorylation	Cho et al. (2011)
Microglia and Tau Pathology	CSF1R	inhibition of CSF1R leads to an attenuation of tau-induced neurodegeneration	Mancuso et al. (2019a); Mancuso et al. (2019b)
	APOE	APOE ε4 markedly exacerbates tau-mediated neurodegeneration	Shi et al. (2017)
	TREM2	loss of TREM2 function promotes seeding and spreading of neuronal plaque tau aggregates.	Leyns et al. (2019)
Microglia and Mitophagy	HMGB1/RAGE signaling pathways	play an important role in blocking late-stage mitophagy in microglia	Zhang et al. (2020)

SR, scavenger receptors; RAGE, the receptor for advanced glycation end products; APOE, Apolipoprotein E; CR1, complement receptor 1; TREM2, triggering receptor expressed on myeloid cells 2; ABCA7, ATP-binding cassette transporter A7; NLRP3, the NOD-like receptor family pyrin domain-containing 3; SOCS, suppressors of cytokine signaling; CX3CR1, CX3C chemokine receptor 1; CSF1R, colony-stimulating factor 1 receptor; HMGB1, the high-mobility group box 1.