Microglia in Alzheimer’s Disease: A Favorable Cellular Target to Ameliorate Alzheimer’s Pathogenesis

Table 2

Microglia in various Alzheimer’s disease preclinical models.

Species/studied material	Experimental model	Effects	References
Complement C3-deficient APP transgenic mouse (APP; C3^-/-)	Mouse model of AD	(i) Increased Aβ levels; (ii) Elevation of fibrillar amyloid plaque burden	[89]
Homozygous C3-deficient and Mac-1-deficient mice (C3^−/−; Mac-1^−/−)	Mouse model of AD	(i) Implicated in the phagocytosis and removal of fAβ by microglia	[91]
hAPP transgenic mouse	Aβ-induced neurotoxicity	(i) Reduced Aβ accumulation	[121]
TLR2 knockdown mice	Aβ42-induced neuroinflammation	(i) Suppressed proinflammatory molecules and integrin markers in microglia	[100]
Mutation of TLR4 in C3H/HeJ mice	Aβ-mediated cognitive dysfunction and neurotoxicity	(i) Reduced microglial activation; (ii) Increase Aβ deposits	[122]
CD36-deficient C57BL/6J mice	Nitro blue tetrazolium induced ROS generation	(i) Decreased microglial recruitment to sites of fAβ; (ii) Reduced the production of ROS, TNF-α, IL-1β, and several chemokines	[110]
RAGE overexpressed mAPP transgenic mice	Mouse model of AD	(i) Increased the production of IL-1β and TNF-α; (ii) Enhanced the infiltration of microglia as well as astrocytes; (iii) Decreased acetylcholine esterase activity and causes Aβ accretion	[115]
Mutation of TLR4 in Mo/Hu APPswe PS1dE9 mice	Amyloidogenesis	(i) Increases in diffuse and fAβ deposits; (ii) Decreased Aβ uptake by microglia	[102]
PS1-APP transgenic mice	Aging induced Aβ deposition	(i) Early microglial enrollment fosters Aβ clearance; (ii) Aβ-mediated inflammation reduces microglial Aβ clearance	[106]
Aged APP23 transgenic mice	Aβ induced neuroinflammation	(i) TREM2 is increased in microglia associated with amyloid plaques; (ii) Lack of extracellular amyloid clearance due to TREM2 signaling	[117]
AD-mutant hAPP transgenic mice	Complement receptor and microglia mediated synaptic loss early in AD	(i) Inhibition of CR3 decreases phagocytic microglia; (ii) Adult brain microglia engulf synaptic material when exposed to soluble Aβ oligomers	[93]
Triple transgenic mice that are deficient in TLR2 (TLR2^−/−)	Aβ42-induced memory impairments	(i) Accelerated spatial and contextual memory impairments; (ii) Increased levels of Aβ	[123]
APP/PS1/SR-A^−/− mice	Aβ induced cognitive decline and neuroinflammation	(i) Increased neuroinflammation; (ii) Elevated Aβ accumulation; (iii) Increased cognitive impairment	[107]