Modulation of inflammation in transgenic models of Alzheimer’s disease

Birch, Amy M; Katsouri, Loukia; Sastre, Magdalena

doi:10.1186/1742-2094-11-25

Journal of Neuroinflammation

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]
PDAPP_SweInd 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]
PDAPP_SweInd 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]
Tau_P301L 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]
PDAPP_SweInd 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	IRAK4^KI/KI	↓Aβ, ↓amyloid plaques, ↓glial activation, ↑PPARγ, ↑IDE, ↑IFNγ, ↓iNOS	[81]
APP/PS1¹	TLR4^Lps-d	↑Aβ, ↑amyloid plaques	[82]
APP/PS1¹	TLR4^Lps-d	↑CD11b⁺ microglia, ↑GFAP	[83]
APP/PS1¹	TLR4^Lps-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]

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.

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ISSN: 1742-2094

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