Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63108, USA.
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Nat Rev Neurosci. 2016 Apr;17(4):201-7. doi: 10.1038/nrn.2016.7. Epub 2016 Feb 25.
Genome-wide association studies have identified rare variants of the gene that encodes triggering receptor expressed on myeloid cells 2 (TREM2) - an immune receptor that is found in brain microglia - as risk factors for non-familial Alzheimer disease (AD). Furthermore, animal studies have indicated that microglia have an important role in the brain response to amyloid-β (Aβ) plaques and that TREM2 variants may have an impact on such a function. We discuss how TREM2 may control the microglial response to Aβ and its impact on microglial senescence, as well as the interaction of TREM2 with other molecules that are encoded by gene variants associated with AD and the hypothetical consequences of the cleavage of TREM2 from the cell surface.
全基因组关联研究已经确定了编码髓系细胞触发受体 2（TREM2）的基因的罕见变体 - TREM2 是一种存在于脑小胶质细胞中的免疫受体 - 是家族性阿尔茨海默病（AD）的风险因素。此外，动物研究表明，小胶质细胞在大脑对淀粉样蛋白-β（Aβ）斑块的反应中起着重要作用，TREM2 变体可能对这种功能有影响。我们讨论了 TREM2 如何控制小胶质细胞对 Aβ的反应及其对小胶质细胞衰老的影响，以及 TREM2 与其他与 AD 相关的基因变异体编码的分子的相互作用，以及 TREM2 从细胞表面被切割的假设后果。
