Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
Mol Neurobiol. 2013 Aug;48(1):180-5. doi: 10.1007/s12035-013-8424-8. Epub 2013 Feb 14.
Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele. The reduced function of TREM2 was speculated to be the main cause in the pathogenic effects of this risk variant, and TREM2 is highly expressed in white matter, as well as in the hippocampus and neocortex, which is partly consistent with the pathological features reported in AD brain, indicating the possible involvement of TREM2 in AD pathogenesis. Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons. TREM2 also participates in the regulation of phagocytic pathways that are responsible for the removal of neuronal debris. In this article, we review the recent epidemiological findings of TREM2 that related with late-onset AD and speculate the possible roles of TREM2 in progression of this disease. Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment.
最近的研究工作表明，髓样细胞表达的触发受体（TREM）2 基因中存在一种罕见的功能变异（R47H），该基因编码 TREM2 蛋白，增加了晚发性阿尔茨海默病（AD）的易感性，其优势比类似于载脂蛋白 E ε4 等位基因。推测 TREM2 的功能降低是该风险变异体致病作用的主要原因，TREM2 在白质以及海马体和新皮层中高度表达，这与 AD 大脑中报道的部分病理特征部分一致，表明 TREM2 可能参与 AD 的发病机制。新出现的证据表明，TREM2 可以通过抑制小胶质细胞介导的细胞因子产生和分泌来抑制炎症反应，从而防止神经元炎症引起的旁观者损伤。TREM2 还参与负责清除神经元碎片的吞噬途径的调节。在本文中，我们回顾了 TREM2 与晚发性 AD 相关的最新流行病学研究结果，并推测了 TREM2 在该疾病进展中的可能作用。基于 TREM2 在 AD 发病机制中的潜在保护作用，靶向 TREM2 可能为 AD 的治疗提供新的机会。
