Hu Shimin, Pan Na, Liu Chunyan, Wang Yuping, Zhang Tingting
Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Key Laboratory of Neuromodulation, Beijing, China.
Front Aging Neurosci. 2021 Nov 12;13:775432. doi: 10.3389/fnagi.2021.775432. eCollection 2021.
Both the genetic and pathological studies link Alzheimer's disease (AD) to the triggering receptor expressed on myeloid cells 2 (TREM2). A large number of studies have explored the value of cerebrospinal fluid (CSF) soluble TREM2 (sTREM2) levels as a biomarker for the diagnosis and prediction of AD; however, the findings are inconsistent. We aimed to review the studies that investigated the association of CSF sTREM2 levels and AD risk, and to provide the recommendations for future research. A systematic literature search was performed using the MEDLINE, EMBASE, and Web of Science (all databases) databases. The meta-analysis for the association between the CSF sTREM2 levels and AD risk included 15 studies (17 comparisons) with a total of 1,153 cases and 1,626 controls. The total results showed that the higher CSF sTREM2 levels and AD risk were associated [standardized mean difference (SMD) = 0.428, 95% (0.213, 0.643), = 81.1%]. However, the analysis of the subgroup of "age difference ≤ 2 years" indicated that sTREM2 was not associated with AD [SMD = 0.090, 95% (-0.092, 0.272), = 27.4%] and had a significantly lower heterogeneity. Combining the results of the "age difference of 5-10 years" [SMD = 0.497, 95% (0.139, 0.855), = 82.5%] and "age difference > 10 years" [SMD = 0.747, 95% (0.472, 1.023), = 50.0%] subgroups showed that the difference in CSF sTREM2 between the AD and control groups was positively correlated with the age difference. A meta-regression analysis showed that the age difference can explain 33.4% of the between-study variance. By conducting further subgroup analyses of the five age-matched studies (495 cases and 364 controls) according to the measurement method, and whether inclusion criteria containing the requirement for pathological evidence of AD, no changes were observed in the corresponding pooled SMD or in the significance of the results. The meta-analysis result of "age difference ≤ 2 years" group was robust in the sensitivity analysis. The available high-quality evidence does not yet support an association between the CSF sTREM2 levels and AD risk. Age matching between the patients with AD and cognitively unimpaired controls was a major influencing factor in the results.
基因研究和病理学研究均将阿尔茨海默病（AD）与髓系细胞触发受体2（TREM2）联系起来。大量研究探讨了脑脊液（CSF）可溶性TREM2（sTREM2）水平作为AD诊断和预测生物标志物的价值；然而，研究结果并不一致。我们旨在回顾调查CSF sTREM2水平与AD风险关联的研究，并为未来研究提供建议。使用MEDLINE、EMBASE和科学网（所有数据库）数据库进行了系统的文献检索。CSF sTREM2水平与AD风险关联的荟萃分析纳入了15项研究（17组比较），共1153例病例和1626例对照。总体结果显示，CSF sTREM2水平较高与AD风险相关[标准化均数差（SMD）=0.428，95%（0.213，0.643），I² = 81.1%]。然而，“年龄差异≤2岁”亚组的分析表明，sTREM2与AD无关[SMD = 0.090，95%（-0.092，0.272），I² = 27.4%]，且异质性显著更低。合并“年龄差异为5 - 10岁”[SMD = 0.497，95%（0.139，0.855），I² = 82.5%]和“年龄差异>10岁”[SMD = 0.747，95%（0.472，1.023），I² = 50.0%]亚组的结果表明，AD组和对照组之间CSF sTREM2的差异与年龄差异呈正相关。荟萃回归分析表明，年龄差异可解释研究间方差的33.4%。根据测量方法以及纳入标准是否包含AD病理证据的要求，对五项年龄匹配研究（495例病例和364例对照）进行进一步亚组分析，相应的合并SMD或结果的显著性均未观察到变化。“年龄差异≤2岁”组的荟萃分析结果在敏感性分析中具有稳健性。现有高质量证据尚不支持CSF sTREM2水平与AD风险之间存在关联。AD患者与认知未受损对照之间的年龄匹配是结果的一个主要影响因素。
