Metabolic phenotyping reveals an emerging role of ammonia abnormality in Alzheimer’s disease

• DOI: 10.1038/s41467-024-47897-y
• Publication Date: 2024-05-07T09:02:00Z
• Authors: Tianlu Chen; Fengfeng Pan; Qi Huang; Guoxiang Xie; Xiaowen Chao; Lirong Wu; Jie Wang; Liang Cui; Tao Sun; Mengci Li; Ying Wang; Yihui Guan; Xiaojiao Zheng; Zhenxing Ren; Yuhuai Guo; Lu Wang; Kejun Zhou; Aihua Zhao; Qihao Guo; Fang Xie; Wei Jia
• Keywords: Abnormality

The metabolic implications in Alzheimer's disease (AD) remain poorly understood. Here, we conducted a metabolomics study on 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, brain amyloid-β deposition 421). These demonstrated synergistic performances across stages subpopulations enhanced the differentiation of AD beyond demographics Apolipoprotein E ε4 allele (APOE-ε4). We validated their eight data sets (total n 7685) obtained from Disease Neuroimaging Initiative (ADNI) Religious Orders Study Memory Aging Project (ROSMAP). Importantly, identified are linked to blood ammonia homeostasis. further confirmed elevated level through development 1060). Our findings highlight as emphasize metabolite-mediated disturbance its potential signature therapeutic target for AD.