TREM2, microglia, and Alzheimer's disease.

1. Mech Ageing Dev. 2021 Apr;195:111438. doi: 10.1016/j.mad.2021.111438. Epub 2021 Jan 28. TREM2, microglia, and Alzheimer's disease. Qin Q(1), Teng Z(2), Liu C(2), Li Q(2), Yin Y(1), Tang Y(3). Author information: (1)Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China. (2)State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. (3)Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China; Neurodegenerative Laboratory of Ministry of Education of the People's Republic of China, Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, China. Electronic address: tangyi@xwhosp.org. Triggering receptor expressed on myeloid cells 2 (TREM2) has been suggested to play a crucial role in Alzheimer's disease (AD) pathogenesis, as revealed by genome-wide association studies (GWAS). Since then, rapidly increasing literature related to TREM2 has focused on elucidating its role in AD pathology. In this review, we summarize our understanding of TREM2 biology, explore TREM2 functions in microglia, address the multiple mechanisms of TREM2 in AD, and raise key questions for further investigations to elucidate the detailed roles and molecular mechanisms of TREM2 in microglial responses. A major breakthrough in our understanding of TREM2 is based on our hypothesis suggesting that TREM2 may act as a multifaceted player in microglial functions in AD brain homeostasis. We conclude that TREM2 can not only influence microglial functions in amyloid and tau pathologies but also participate in inflammatory responses and metabolism, acting alone or with other molecules, such as apolipoprotein E (APOE). This review provides novel insight into the broad role of TREM2 in microglial function in AD and enables us to develop new strategies aimed at the immune system to treat AD pathogenesis. Copyright © 2021 Elsevier B.V. All rights reserved. DOI: 10.1016/j.mad.2021.111438 PMID: 33516818 [Indexed for MEDLINE]