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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

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 Wen, Huaxi Xu, Guojun Bu, Xiao-Fen Chen

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. More... »

PAGES

1365

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-09118-9

    DOI

    http://dx.doi.org/10.1038/s41467-019-09118-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112969706

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30911003


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