Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model

Li Zhong, Ying Xu, Rengong Zhuo, Tingting Wang, Kai Wang, Ruizhi Huang, Daxin Wang, Yue Gao, Yifei Zhu, Xuan Sheng, Kai Chen, Na Wang, Lin Zhu, Dan Can, Yuka Marten, Mitsuru Shinohara, Chia-Chen Liu, Dan Du, Hao Sun, Lei WenHuaxi Xu, Guojun D Bu, Xiao Fen Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer’s disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy.

Original languageEnglish (US)
Article number1365
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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phenotype
Myeloid Cells
Amyloid
Alzheimer Disease
Amyloid Plaques
Phenotype
cells
cerebrospinal fluid
Cerebrospinal fluid
Dependovirus
Long-Term Potentiation
Direct injection
pathology
Microglia
Neuroprotective Agents
viruses
Pathology
Viruses
toxicity
markers

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. / Zhong, Li; Xu, Ying; Zhuo, Rengong; Wang, Tingting; Wang, Kai; Huang, Ruizhi; Wang, Daxin; Gao, Yue; Zhu, Yifei; Sheng, Xuan; Chen, Kai; Wang, Na; Zhu, Lin; Can, Dan; Marten, Yuka; Shinohara, Mitsuru; Liu, Chia-Chen; Du, Dan; Sun, Hao; Wen, Lei; Xu, Huaxi; Bu, Guojun D; Chen, Xiao Fen.

In: Nature communications, Vol. 10, No. 1, 1365, 01.12.2019.

Research output: Contribution to journalArticle

Zhong, L, Xu, Y, Zhuo, R, Wang, T, Wang, K, Huang, R, Wang, D, Gao, Y, Zhu, Y, Sheng, X, Chen, K, Wang, N, Zhu, L, Can, D, Marten, Y, Shinohara, M, Liu, C-C, Du, D, Sun, H, Wen, L, Xu, H, Bu, GD & Chen, XF 2019, 'Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model', Nature communications, vol. 10, no. 1, 1365. https://doi.org/10.1038/s41467-019-09118-9
Zhong, Li ; Xu, Ying ; Zhuo, Rengong ; Wang, Tingting ; Wang, Kai ; Huang, Ruizhi ; Wang, Daxin ; Gao, Yue ; Zhu, Yifei ; Sheng, Xuan ; Chen, Kai ; Wang, Na ; Zhu, Lin ; Can, Dan ; Marten, Yuka ; Shinohara, Mitsuru ; Liu, Chia-Chen ; Du, Dan ; Sun, Hao ; Wen, Lei ; Xu, Huaxi ; Bu, Guojun D ; Chen, Xiao Fen. / Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. In: Nature communications. 2019 ; Vol. 10, No. 1.
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abstract = "Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer’s disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy.",
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AU - Xu, Ying

AU - Zhuo, Rengong

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AU - Wang, Kai

AU - Huang, Ruizhi

AU - Wang, Daxin

AU - Gao, Yue

AU - Zhu, Yifei

AU - Sheng, Xuan

AU - Chen, Kai

AU - Wang, Na

AU - Zhu, Lin

AU - Can, Dan

AU - Marten, Yuka

AU - Shinohara, Mitsuru

AU - Liu, Chia-Chen

AU - Du, Dan

AU - Sun, Hao

AU - Wen, Lei

AU - Xu, Huaxi

AU - Bu, Guojun D

AU - Chen, Xiao Fen

PY - 2019/12/1

Y1 - 2019/12/1

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