非痴呆人群脑脊液可溶性TREM-1与阿尔茨海默病生物标志物及认知功能的关系  

Correlation of soluble triggering receptor expressed on myeloid cells-1 in cerebrospinal fluid with Alzheimer’s disease biomarkers and cognitive function in non-dementia individuals

作　　者：郭海华 王会福[2] GUO Haihua;WANG Huifu(Qingdao Medical College of Qingdao University,Qingdao 266071,China)

机构地区：[1]青岛大学青岛医学院,山东青岛266071 [2]青岛市市立医院神经内科

出　　处：《精准医学杂志》2025年第2期112-116,共5页Journal of Precision Medicine

基　　金：中国科技创新2023-“脑科学与类脑研究”重大项目(2022ZD0211600)。

摘　　要：目的探讨非痴呆人群脑脊液(CSF)中可溶性髓系细胞触发受体-1(sTREM-1)与阿尔茨海默病(Alzheimer’s disease,AD)核心生物标志物及认知功能的关系。方法从阿尔茨海默病神经影像学计划(ADNI)研究队列中纳入558例非痴呆者作为研究对象,收集所有研究对象的基本人口统计学特征及CSF中神经炎症标志物sTREM-1、淀粉样蛋白-β42(Aβ42)、总tau(t-tau)和磷酸化tau(p-tau)等指标的水平,以及简易智力状态检查(MMSE)及蒙特利尔认知评估(MoCA)评分等认知功能指标。采用多元线性回归分析研究对象CSF中sTREM-1与AD核心生物标志物及认知功能间是否存在线性关联,随后进行中介分析探讨CSF中AD核心生物标志物是否中介了CSF中sTREM-1与认知功能的关系。结果多元线性回归结果显示,CSF中sTREM-1水平与研究对象MMSE、MoCA评分呈负相关(P<0.05),与CSF中p-tau水平、t-tau水平、p-tau/Aβ42比值及t-tau/Aβ42比值呈正相关(P<0.05),而与CSF中Aβ42水平无关(P>0.05)。中介分析结果显示,CSF中p-tau和t-tau中介了CSF中sTREM-1与认知功能间关系。结论非痴呆人群CSF中sTREM-1水平与CSF中t-tau及p-tau水平呈正相关,神经炎症可能主要通过影响神经元中tau蛋白的异常磷酸化和聚集,从而参与AD发病及患者认知下降过程。Objective To investigate the correlation of soluble triggering receptor expressed on myeloid cells-1(sTREM-1)in cerebrospinal fluid(CSF)with core Alzheimer’s disease(AD)biomarkers and cognitive function in non-dementia individuals.Methods A total of 558 non-dementia individuals in the Alzheimer’s Disease Neuroimaging Initiative cohort were enrolled as subjects,and related indicators were collected,including demographic features,the levels of neuroinflammatory marker sTREM-1,amyloid-β42(Aβ42),total tau(t-tau),and phosphorylated tau(p-tau)in CSF,and cognitive function scores assessed by Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA).A multiple linear regression analysis was used to investigate the linear correlation between sTREM-1 in CSF and core AD biomarkers and cognitive function,and the mediation analysis was used to explore whether the core AD biomarkers in CSF mediated the association between sTREM-1 and cognitive function.Results The multiple linear regression analysis showed that the level of sTREM-1 in CSF was negatively correlated with MMSE and MoCA scores(P<0.05)and was positively correlated with p-tau,t-tau,p-tau/Aβ42 ratio,and t-tau/Aβ42 ratio in CSF(P<0.05),while it was not significantly correlated with the level of Aβ42 in CSF(P>0.05).The mediation analysis showed that p-tau and t-tau in CSF mediated the association between sTREM-1 and cognitive function.Conclusion In non-dementia individuals,the level of sTREM-1 in CSF is positively correlated with the levels of t-tau and p-tau in CSF.Neuroinflammation is involved in the pathogenesis of AD and the process of cognitive decline by affecting abnormal phosphorylation and aggregation of tau protein in neurons.

关 键 词：阿尔茨海默病 认知功能障碍 Tau病变 髓系细胞触发受体-1 生物标记 

分 类 号：R745.7[医药卫生—神经病学与精神病学]