Soluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer's disease.
Soluble TREM2 levels associate with conversion from mild cognitive impairment to Alzheimer's disease.
复制标题
可溶性 TREM2 水平与轻度认知障碍向阿尔茨海默病的转变相关
DOI：
10.1172/jci158708
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发表时间：
2022-12-15
影响因子：
15.9
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Zhao, Aonan;Jiao, Yang;Ye, Guanyu;Kang, Wenyan;Tan, Lan;Li, Yuanyuan;Deng, Yulei;Liu, Jun
髓样细胞可溶性触发受体2（sTREM 2）在阿尔茨海默病（AD）病理性β淀粉样蛋白（Aβ）的清除中起重要作用。本研究旨在探讨sTREM 2作为轻度认知功能障碍（MCI）向AD转化的中枢和外周预测因子。分析了ADNI数据库中健康对照（HC）、MCI患者和AD患者的脑脊液（CSF）和氟倍他平-PET（AV 45）图像中的sTREM 2和Aβ1-42水平。测定瑞金医院阿尔茨海默病（NRHAD）队列神经病学数据库中的外周血浆sTREM 2和Aβ1-42水平，并在随访时对MCI患者进行重新评估，以评估进展为AD。在中国阿尔茨海默病生物标志物和生活方式（CABLE）数据库的数据中分析CSF和血浆sTREM 2水平之间的关联。结果显示，CSF sTREM 2和Aβ1-42水平低的MCI患者更容易发展为AD。在Aβ沉积阳性的受试者中，通过AV 45成像评估，CSF sTREM 2水平升高与MCI向AD转化的风险降低相关。同时，在NRHAD队列中，血浆中sTREM 2水平高的MCI组个体患AD的风险更高，而血浆中sTREM 2水平高的低Aβ1-42与更快的认知下降相关。此外，CSF sTREM 2水平与CABLE数据库中的血浆sTREM 2水平高度相关。这些发现表明，sTREM 2可用作MCI向AD转化的潜在预测生物标志物。本研究得到了国家自然科学基金的赠款（grant nos. 82001341、82071415、81873778和82201392）;上海帆船计划（批准号22 YF 1425100）;和中国博士后科学基金资助项目（批准号2021 M702169）。
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) plays an important role in the clearance of pathological amyloid-β (Aβ) in Alzheimer’s disease (AD). This study aimed to explore sTREM2 as a central and peripheral predictor of the conversion from mild cognitive impairment (MCI) to AD. sTREM2 and Aβ1–42 levels in cerebrospinal fluid (CSF) and florbetapir-PET (AV45) images were analyzed for healthy control (HCs), patients with MCI, and patients with AD from the ADNI database. Peripheral plasma sTREM2 and Aβ1–42 levels were determined for our Neurology database of Ruijin Hospital for Alzheimer’s Disease (NRHAD) cohort, and patients with MCI were reevaluated at follow-up visits to assess for progression to AD. The association between CSF and plasma sTREM2 levels was analyzed in data from the Chinese Alzheimer’s Biomarker and Lifestyle (CABLE) database. The results showed that patients with MCI who had low levels of CSF sTREM2 and Aβ1–42 were more likely to develop AD. Among participants with positive Aβ deposition, as assessed by AV45 imaging, elevated CSF sTREM2 levels were associated with a decreased risk of MCI-to-AD conversion. Meanwhile, in the NRHAD cohort, individuals in the MCI group with high sTREM2 levels in plasma were at a greater risk for AD, whereas low Aβ1–42 with high sTREM2 levels in plasma were associated with a faster cognitive decline. In addition, CSF sTREM2 levels were highly correlated with plasma sTREM2 levels in the CABLE database. These findings suggest that sTREM2 may be useful as a potential predictive biomarker of MCI-to-AD conversion. This study was supported by grants from the National Natural Science Foundation of China (grant nos. 82001341, 82071415, 81873778, and 82201392); the Shanghai Sailing Program (grant no. 22YF1425100); and the China Postdoctoral Science Foundation funded project (grant no. 2021M702169).