On March 25, a research team from the School of Medicine, Xiamen University led by Prof. Xiao-Fen Chen published a paper entitled Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model in Nature Communications (DOI: 10.1038/s41467-019-09118-9).
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most prominent cause of dementia in the elderly population. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for AD. A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels in the cerebrospinal fluid correlates with AD progression. To gain insights into the pathological roles of sTREM2, the authors 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. They 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, supporting an indispensable role of microglia in sTREM2 function. The study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity, and suggests that increasing sTREM2 can be explored for AD therapy.
Research by the authors was supported by grants from the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province, the Fundamental Research Funds for the Central Universities, the Alzheimer's Association, the Postdoctoral Science Foundation of China and the Natural Science Foundation of Fujian Province.