Modulation of inflammation in transgenic models of Alzheimer’s disease

Table 1 Modulation of inflammatory mediators in Alzheimer’s disease mouse models

AD mouse model	Genetic manipulation	Effect on Alzheimer-like pathology	Reference
APP23¹	TNF-RI−/−	↓Aβ, ↓amyloid plaques, ↓microglial activation, ↓BACE1, ↓neuronal loss, ↑memory	[21]
3xTg-AD²	TNF-RI/RII−/−	↑Aβ, ↑amyloid plaques, ↑PHF, ↓IBA1, ↓microglial phagocytosis, ↓LTP	[24]
3xTg-AD²	TNFα−/−	↑Aβ, ↔memory improvement	[25]
3xTg-AD²	TgIL-1β^XAT	↓Aβ, ↑p-tau, ↑glial activation	[26]
APP/PS1³	TgIL-1β^XAT	↓Aβ, ↑glial activation, ↑cytokines	[27]
APP/PS1³	TgIL-1β^XAT	↓Aβ, ↓amyloid plaques	[28]
APP/PS1⁴	IL-12α−/−	↓Aβ	[19]
APP/PS1⁴	IL-12β−/−	↓Aβ, ↓glial activation	[19]
APP/PS1⁴	IL-23−/−	↓Aβ	[19]
PDGF-APP_SweInd line J9⁵	GFAP-TGFβ1	↓Aβ, ↑cerebrovascular Aβ, ↑glial activation	[29]
PDAPP⁶	GFAP-TGFβ1	↑cerebrovascular Aβ, ↑CAA, ↑perivascular astrocytes	[30]
Tg2576⁷	CD11c-DNR(TGF-β)	↓Aβ, ↓memory impairment, ↓CAA	[31]
Tg2576⁷	IFNγRI−/−	↓Aβ, ↓glial activation	[20]
APP/PS1³	Mrp14−/−	↓Aβ, ↓BACE1, ↓cytokines, ↑microglial activation, ↑Aβ phagocytosis	[32]
Tg2576⁷	NOS2−/−	↑Aβ,↑p-tau, ↑neuronal death	[17]
APP/PS1³	NOS2−/−	↓Aβ, ↓plaques, ↑LTP, ↑memory	[18]
APP/PS1³	NOS2−/−	↑IDE	[33]
Tg-SwDI/B⁸	NOS2−/−	↔Aβ, ↑p-tau, ↑CAA, ↑neuronal loss, ↑memory impairment	[34]
PDGF-APP_SweInd line J9⁵	PDGF-RAGE	↑Aβ, ↑glial activation, ↓LTP	[35]
PDGF-APP_SweInd line J9⁵	GFAP-α1-ACT	↑Aβ	[36]
PDAPP⁶	GFAP-α1-ACT	↑Aβ, ↑plaques	[37]
PDAPP⁶	GFAP-α1-ACT	↑p-tau	[38]

¹hAPP Swedish mutation under the murine Thy1.2 promoter. ²hAPP Swedish, hPS1 knock-in with M146V mutation, htau P301L mutation. APP and Tau are under the Thy1 promoter. ³hAPP Swedish and hPS1dE9 mutations under the murine Thy1.2 promoter. ⁴hAPP Swedish and hPS1 L166P mutations under the murine Thy1 promoter. ⁵hAPP Swedish and Indiana mutations under the PDGF promoter. ⁶hAPP Indiana mutation under the PDGF promoter. ⁷hAPP Swedish mutation under the hamster prion promoter. ⁸hAPP Swedish, Dutch and Iowa mutations under the murine Thy1.2 promoter. Aβ, amyloid-beta; ACT, antichymotrypsin; AD, Alzheimer’s disease; APP, amyloid precursor protein; CAA, cerebral amyloid angiopathy; GFAP, glial fibrillary acidic protein; IBA, ionized calcium binding adaptor molecule-1; IDE, insulin degrading enzyme; IFN, interferon; IL, interleukin; LTP, long-term potentiation; NOS, nitric oxide synthase; PDAPP, amyloid precursor protein under control of platelet-derived growth factor promoter; PDGF, platelet-derived growth factor; PHF, Paired helical filament; RAGE, Receptor for Advanced Glycation End; Tg, transgenic; TGF, transforming growth factor; TNF, tumor necrosis factor.

ISSN: 1742-2094