Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China.
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.
Mech Ageing Dev. 2021 Apr;195:111438. doi: 10.1016/j.mad.2021.111438. Epub 2021 Jan 28.
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.
髓系细胞触发受体 2（TREM2）已被认为在阿尔茨海默病（AD）发病机制中发挥关键作用，这是通过全基因组关联研究（GWAS）揭示的。从那时起，与 TREM2 相关的文献迅速增加，重点研究其在 AD 病理学中的作用。在这篇综述中，我们总结了我们对 TREM2 生物学的理解，探讨了 TREM2 在小胶质细胞中的功能，解决了 TREM2 在 AD 中的多种机制，并提出了进一步研究的关键问题，以阐明 TREM2 在小胶质细胞反应中的详细作用和分子机制。我们对 TREM2 的理解的一个重大突破是基于我们的假设，即 TREM2 可能在 AD 大脑稳态中小胶质细胞功能中发挥多方面的作用。我们得出的结论是，TREM2 不仅可以影响淀粉样蛋白和 tau 病理学中小胶质细胞的功能，还可以参与炎症反应和代谢，单独或与载脂蛋白 E（APOE）等其他分子一起发挥作用。这篇综述为 TREM2 在 AD 中小胶质细胞功能中的广泛作用提供了新的见解，并使我们能够制定旨在针对免疫系统治疗 AD 发病机制的新策略。
