PDF(Pubmed)
Abstract：
The metabolic implications in Alzheimer\'s disease (AD) remain poorly understood. Here, we conducted a metabolomics study on a moderately aging Chinese Han cohort (n = 1397; mean age 66 years). Conjugated bile acids, branch-chain amino acids (BCAAs), and glutamate-related features exhibited strong correlations with cognitive impairment, clinical stage, and brain amyloid-β deposition (n = 421). These features demonstrated synergistic performances across clinical stages and subpopulations and enhanced the differentiation of AD stages beyond demographics and Apolipoprotein E ε4 allele (APOE-ε4). We validated their performances in eight data sets (total n = 7685) obtained from Alzheimer\'s Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Memory and Aging Project (ROSMAP). Importantly, identified features are linked to blood ammonia homeostasis. We further confirmed the elevated ammonia level through AD development (n = 1060). Our findings highlight AD as a metabolic disease and emphasize the metabolite-mediated ammonia disturbance in AD and its potential as a signature and therapeutic target for AD.
摘要：
对阿尔茨海默病（AD）的代谢影响仍知之甚少。这里,我们对一个中度老龄化的中国汉族队列(n=1397;平均年龄66岁)进行了代谢组学研究.共轭胆汁酸，支链氨基酸（BCAAs），谷氨酸相关特征与认知障碍表现出很强的相关性，临床分期,和脑淀粉样β沉积（n=421）。这些特征显示了跨临床阶段和亚群的协同表现，并增强了人口统计学和载脂蛋白Eε4等位基因（APOE-ε4）以外的AD阶段的分化。我们在阿尔茨海默病神经影像学计划（ADNI）和宗教秩序研究以及记忆与衰老项目（ROSMAP）获得的八个数据集（总共n=7685）中验证了他们的表现。重要的是,确定的特征与血氨稳态有关。我们通过AD发展进一步证实了升高的氨水平(n=1060)。我们的发现强调了AD是一种代谢性疾病，并强调了AD中代谢物介导的氨紊乱及其作为AD特征和治疗靶标的潜力。
