Meng Yuchi, Cheng Murong, Qu Hongyan, Song Zhenxue, Zhang Ling, Zeng Yuanjun, Zhang Dongfeng, Li Suyun
Department of Epidemiology and Health Statistics, School of Public Health, Qingdao University, Qingdao, Shandong, China.
Front Aging Neurosci. 2024 Dec 18;16:1511437. doi: 10.3389/fnagi.2024.1511437. eCollection 2024.
Previous research has suggested a link between the onset of Alzheimer's disease (AD) and metabolic disorder; however, the findings have been inconsistent. To date, the majority of metabolomics studies have focused on AD, resulting in a relative paucity of research on early-stage conditions such as mild cognitive impairment (MCI) underexplored. In this study, we employed a comprehensive platform for the early screening of individuals with MCI using high-throughput targeted metabolomics.
We included 171 participants including 124 individuals with MCI and 47 healthy subjects. Univariate statistical analysis was conducted using -tests or Wilcoxon rank-sum tests, with -values corrected by the Benjamini-Hochberg method. The screening criteria were set at FDR < 0.05 and fold change (FC) > 1.5 or < 0.67. Multivariate analysis was performed using orthogonal partial least squares discriminant analysis (OPLS-DA), where differential metabolites were identified based on variable influence on projection (VIP) scores (VIP > 1 and FDR < 0.05). Random forest analysis was used to further evaluate the ability of the metabolic data to distinguish effectively between the two groups.
A total of 14 differential metabolites were identified, leading to the discovery of a biomarker panel consisting of three plasma metabolites including uric acid, pyruvic acid and isolithocholic acid that effectively distinguished MCI patients from healthy subjects.
These findings have provided a comprehensive metabolic profile, offering valuable insights into the early prediction and understanding of the pathogenic processes underlying MCI. This study holds the potential for advancing early detection and intervention strategies for MCI.
先前的研究表明阿尔茨海默病(AD)的发病与代谢紊乱之间存在联系;然而,研究结果并不一致。迄今为止,大多数代谢组学研究都集中在AD上,导致对轻度认知障碍(MCI)等早期病症的研究相对较少,尚未得到充分探索。在本研究中,我们采用了一个综合平台,利用高通量靶向代谢组学对MCI个体进行早期筛查。
我们纳入了171名参与者,包括124名MCI个体和47名健康受试者。使用t检验或Wilcoxon秩和检验进行单变量统计分析,P值采用Benjamini-Hochberg方法校正。筛选标准设定为错误发现率(FDR)<0.05且倍数变化(FC)>1.5或<0.67。使用正交偏最小二乘判别分析(OPLS-DA)进行多变量分析,根据变量投影重要性(VIP)得分(VIP>1且FDR<0.05)识别差异代谢物。随机森林分析用于进一步评估代谢数据有效区分两组的能力。
共鉴定出14种差异代谢物,从而发现了一个由三种血浆代谢物组成的生物标志物组,包括尿酸、丙酮酸和异石胆酸,它们能有效区分MCI患者和健康受试者。
这些发现提供了一个全面的代谢概况,为早期预测和理解MCI潜在的致病过程提供了有价值的见解。本研究具有推进MCI早期检测和干预策略的潜力。