TREM2 Overexpression has No Improvement on Neuropathology and Cognitive Impairment in Aging APPswe/PS1dE9 Mice

Molecular Neurobiology
T JiangJin-Tai Yu

Abstract

Previously, we showed that overexpression of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific immune receptor, in the brain of a middle-aged (7 months old) APPswe/PS1dE9 mice could ameliorate Alzheimer's disease (AD)-related neuropathology by enhancement of microglial amyloid-β (Aβ) phagocytosis. Since AD is an age-related neurodegenerative disorder, it is critical to assess the efficacy of TREM2 overexpression in aging animals with an advanced disease stage. In vivo, we employed a lentiviral strategy to overexpress TREM2 in the brain of aging (18 months old) APPswe/PS1dE9 mice, and observed its efficacy on AD-related neuropathology and cognitive functions. Afterwards, we directly isolated microglia from middle-aged and aging APPswe/PS1dE9 mice and determined effects of TREM2 overexpression on microglial Aβ phagocytosis and Aβ-binding receptors expression in vitro. In aging APPswe/PS1dE9 mice, TREM2 overexpression has no beneficial effect on AD-related neuropathology and spatial cognitive functions. Of note, in vitro experiments showed a significant reduction of Aβ phagocytosis in microglia from aging APPswe/PS1dE9 mice, possibly attributing to the declined expression of Aβ-binding receptors. Meanw...Continue Reading

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Citations

Jun 14, 2016·Expert Review of Neurotherapeutics·William James Deardorff, George T Grossberg
Oct 22, 2016·Acta Neuropathologica·Teng JiangJin-Tai Yu
May 17, 2017·Journal of Alzheimer's Disease : JAD·Jin-Bao ZhuJin-Tai Yu
Jun 12, 2018·Expert Opinion on Therapeutic Targets·Yuetiva DemingCarlos Cruchaga
Aug 5, 2017·Molecular Neurodegeneration·Taylor R JayGary E Landreth
Mar 28, 2018·Journal of Internal Medicine·R Loera-ValenciaP Nilsson
Apr 16, 2018·Journal of Neuroinflammation·Jiang-Tao Li, Ying Zhang
Dec 3, 2020·International Journal of Molecular Sciences·Anna ChiariniIlaria Dal Prà
Apr 4, 2021·International Journal of Molecular Sciences·Mehdi EshraghiSaeid Ghavami
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Qiuju YuanZhi-Xiu Lin
Sep 16, 2021·FEBS Open Bio·Yuumi OkuzonoShuji Sato

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Methods Mentioned

BETA
transgenic
ELISA
flow cytometry
transfection
glycosylation

Software Mentioned

Quantity One
ImageJ
ARRIVE

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