Data_Sheet_1_Association of soluble TREM2 with Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis.docx

ObjectiveSoluble triggering receptor expressed on myeloid cells 2 (sTREM2) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Previous studies have produced inconsistent results regarding sTREM2 levels in various clinical stages of AD. This study aims to establish the correlation between sTREM2 levels and AD progression through a meta-analysis of sTREM2 levels in cerebrospinal fluid (CSF) and blood.
MethodsComprehensive searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify observational studies reporting CSF and blood sTREM2 levels in AD patients, MCI patients, and healthy controls. A random effects meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs).
ResultsThirty-six observational studies involving 3,016 AD patients, 3,533 MCI patients, and 4,510 healthy controls were included. CSF sTREM2 levels were significantly higher in both the AD [SMD = 0.28, 95% CI (0.15, 0.41)] and MCI groups [SMD = 0.30, 95% CI (0.13, 0.47)] compared to the healthy control group. However, no significant differences in expression were detected between the AD and MCI groups [SMD = 0.09, 95% CI (−0.09, 0.26)]. Furthermore, increased plasma sTREM2 levels were associated with a higher risk of AD [SMD = 0.42, 95% CI (0.01, 0.83)].
ConclusionCSF sTREM2 levels are positively associated with an increased risk of AD and MCI. Plasma sTREM2 levels were notably higher in the AD group than in the control group and may serve as a promising biomarker for diagnosing AD. However, sTREM2 levels are not effective for distinguishing between different disease stages of AD. Further investigations are needed to explore the longitudinal changes in sTREM2 levels, particularly plasma sTREM2 levels, during AD progression.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024514593

研究背景与目的
可溶性髓系细胞触发受体2（soluble triggering receptor expressed on myeloid cells 2, sTREM2）是一种潜在的神经炎症生物标志物，与阿尔茨海默病（Alzheimer’s disease, AD）及轻度认知障碍（mild cognitive impairment, MCI）的发病机制密切相关。既往针对AD不同临床阶段患者sTREM2水平的研究结果并不一致。本研究拟通过对脑脊液（cerebrospinal fluid, CSF）及血液中sTREM2水平开展荟萃分析，明确sTREM2水平与AD进展的相关性。

研究方法
本研究在PubMed、Embase、Web of Science及考克兰文库（Cochrane Library）中进行全面检索，筛选报道AD患者、MCI患者及健康对照者脑脊液与血液sTREM2水平的观察性研究。采用随机效应模型荟萃分析计算标准化均数差（standardized mean difference, SMD）及95%置信区间（confidence intervals, CIs）。

研究结果
本研究共纳入36项观察性研究，涉及3016例AD患者、3533例MCI患者及4510例健康对照者。与健康对照组相比，AD组[SMD=0.28, 95%CI(0.15, 0.41)]与MCI组[SMD=0.30, 95%CI(0.13, 0.47)]的脑脊液sTREM2水平均显著升高。但AD组与MCI组之间的sTREM2表达水平无显著差异[SMD=0.09, 95%CI(-0.09, 0.26)]。此外，血浆sTREM2水平升高与AD发病风险增加相关[SMD=0.42, 95%CI(0.01, 0.83)]。

研究结论
脑脊液sTREM2水平与AD及MCI的发病风险呈正相关。AD患者的血浆sTREM2水平显著高于健康对照组，其或可作为诊断AD的潜在有效生物标志物。但sTREM2水平无法有效区分AD的不同疾病阶段。未来仍需开展进一步研究，探索AD进展过程中sTREM2水平（尤其是血浆sTREM2水平）的纵向变化特征。

系统评价注册
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024514593