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Table 2 Modulation of glia in Alzheimer’s disease mouse models

From: Modulation of inflammation in transgenic models of Alzheimer’s disease

AD mouse model Genetic manipulation Effect on Alzheimer-like pathology Reference
APP/PS11 Scara1−/− ↑Aβ, ↑mortality, ↓IDE, ↓Neprilysin [64]
PDAPPSweInd line J202 Scarb1−/− ↑amyloid plaques, ↑CAA, ↔glial activation, ↑memory impairment [65]
APP/PS13 CD11b-TK ↔Aβ, ↔amyloid plaques, ↑GFAP, ↓Iba1 [55]
APP234 CD11b-TK ↓Aβ, ↓Iba1, ↔amyloid plaques [55]
PDAPPSweInd line J202 CxCR3-GFP ki ↔Aβ, ↑microglial activation, ↑IL-6, ↑TNF-α, ↑p-tau, ↑memory impairment [62]
TgCRND85 CxCR3-GFP ki ↓Aβ, ↓amyloid plaques, ↑ microglial phagocytosis, ↑microglial proliferation [59]
APP/PS13 CxCR3-GFP ki ↓Aβ, ↓amyloid plaques, ↓microglia, ↑ microglial phagocytosis [60]
R1.406 CxCR3-GFP ki ↓Aβ, ↓amyloid plaques [60]
htau7 CxCR3-GFP ki ↑p-tau, ↑Gallyas-positive dystrophic neurites, ↓Iba1, ↑microglial activation (CD68+ and CD45+) [66]
3xTg-AD8 CxCR3-GFP ki ↓neuronal loss [61]
Tg25769 Ccr2−/− ↑Aβ, ↓NEP [67]
APP/PS110 Ccr2−/− ↑soluble Aβ, ↑microglial activation, ↑memory impairment [68]
APP/PS110 NSE-COX2 ↑Aβ, ↑PGE2 [69]
Tg25769 C1q−/− ↔Aβ, ↓glial activation, ↑neuronal degeneration [70]
Tg25769 C1q−/− ↔Aβ, ↓glial activation, ↓loss of synaptic markers [71]
APP/PS111 C1q−/− ↔Aβ, ↓glial activation [71]
TauP301L line JNLP312 sCrry ↑p-tau [49]
Tg25769 CD40L−/− ↓p-tau [72]
Tg25769 CD40L−/− ↓Aβ, ↓glial activation [73, 74]
APP/PS111 CD40L−/− ↓Aβ, ↓glial activation [73]
APP/PS11 Nlrp3−/− ↓Aβ, ↓plaques, ↓IL-1β, ↓iNOS, ↑LTP, ↑spatial memory, ↑IDE [39]
PDAPPSweInd line J202 C3−/− ↑Aβ, ↑amyloid plaques, ↑glial activation, ↑neuronal loss [75]
APP/PS11 CD14−/− ↓Aβ, ↓amyloid plaques, ↓CD45+ activated microglia [76]
APP/PS11 CD33−/− ↓Aβ, ↓plaques [77]
Tg25769 (before plaque onset) CD36−/− ↔Aβ, ↔ROS [78]
Tg25769 (old mice) CD36−/− ↓Aβ40, ↓CAA, ↑cognitive performance [79]
APP/PS11 CD45−/− ↑Aβ, ↑amyloid plaques, ↑inflammatory microglia, ↑TNF-α, ↑IL-1β, ↑neuronal death [80]
APP/PS13 IRAK4KI/KI ↓Aβ, ↓amyloid plaques, ↓glial activation, ↑PPARγ, ↑IDE, ↑IFNγ, ↓iNOS [81]
APP/PS11 TLR4Lps-d ↑Aβ, ↑amyloid plaques [82]
APP/PS11 TLR4Lps-d ↑CD11b+ microglia, ↑GFAP [83]
APP/PS11 TLR4Lps-d ↑Aβ, ↑ amyloid plaques, ↓microglial activation, ↑cognitive impairment [84]
APP/PS11 MyD88−/− ↓Aβ, ↓amyloid plaques, ↓CD11b+, CD45+ microglia [85]
APP/PS110 MyD88+/− ↓amyloid plaques, ↑soluble Aβ, ↓IL-1β [86]
APP/PS110 TLR2−/− Delayed plaque formation, ↑Aβ, ↑TGF-β, ↑memory impairment [87]
Tg25769 GFAP-MCP1 ↑Aβ, ↑microglial activation [88]
APP/PS11 GFAP−/−Vim−/− ↑Aβ, ↑amyloid plaques, ↑neurotic dystrophy, ↓activated astrocytes, ↑microglia, [89]
  1. 1hAPP Swedish and hPS1dE9 mutations under the murine Thy1.2 promoter. 2hAPP Swedish and Indiana mutations under the PDGF promoter. 3hAPP Swedish and hPS1 L166P mutation under the Thy1 promoter. 4hAPP Swedish mutation under the murine Thy1.2 promoter. 5hAPP Swedish and Indiana mutations under the hamster prion promoter. 6YAC with 300Kb hAPP gene with the Swedish mutation. 7 Mapt−/− mice crossed with Tg(MAPT)8cPdav that contains the whole 5′-flanking and exons 1–14 of the hMAPT gene. 8hAPP Swedish mutation, hPS1 knock-in with M146V mutation, htau P301L mutation. hAPP and hTau are under the Thy1 promoter. 9hAPP Swedish mutation under the hamster prion promoter. 10hAPP Swedish mutation and hPS1 with the A246E mutation both under the mouse prion promoter. 11Tg2576 (hAPP Swedish mutation) crossed with hPS1 with the M146L mutation. 12hTau with the P301L mutation under the mouse prion promoter. Aβ, amyloid-beta; AD, Alzheimer’s disease; APP, amyloid precursor protein; CAA, cerebral amyloid angiopathy; GFAP, glial fibrillary acidic protein; GFP, green Fluorescent Protein; IBA, ionized calcium binding adaptor molecule-1; IDE, insulin degrading enzyme; IFN, interferon; IL, interleukin; iNOS, inducible nitric oxide synthase; LTP, long-term potentiation; MyD88, myeloid differentiation primary response protein 88; NSE-COX2, neuron-specific enolase-cyclooxigenase-2; PDAPP, amyloid precursor protein under control of platelet-derived growth factor promoter; PDGF, platelet-derived growth factor; PGE2, prostaglandin E2; PHF, Paired helical filament; PPAR, peroxisome proliferator-activated receptor; RAGE, Receptor for Advanced Glycation End; ROS, reactive oxygen species; Scar, scavenger receptor; Tg, transgenic; TGF, transforming growth factor; TLR, Toll-like receptor; TNF, tumor necrosis factor.