多组学分析探索阿尔茨海默病神经影像学倡议队列中的血液代谢生物标志物。
Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer's Disease Neuroimaging Initiative cohort.
机构信息
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Human Biology Integration Foundation, Eisai Co., Ltd., Ibaraki, Japan.
出版信息
Sci Rep. 2024 Apr 2;14(1):6797. doi: 10.1038/s41598-024-56837-1.
Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10 and 4.3 × 10). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD.
阿尔茨海默病(AD)是一种常见的神经退行性疾病,通常会导致痴呆。因此,识别 AD 的早期生物标志物成为一种新兴需求,因为大脑功能障碍在临床症状出现前 20 年就开始了。为此,我们使用 MS-DIAL 重新分析了来自 AD 神经影像学倡议(ADNI)队列的 905 名患者的非靶向代谢组学质谱数据,共分析了 39108 种独特生物分子的 1304633 张光谱。确定了 93 种亲水性代谢物的代谢谱。此外,我们还整合了靶向脂质组学数据(来自 1524 名患者的 4873 个样本),以探索用于预测在两年内被诊断为 AD 的患者进行性轻度认知障碍(pMCI)的候选生物标志物。与其他患者相比,具有较低水平乙硫氨酸的患者 AD 进展率高 12%,其显著性为 P=0.012(Wald 检验)。此外,在 AD 患者中证实了神经节苷脂(GM3)的增加和质体脂质的减少,其中许多与载脂蛋白 E 多态性有关,并且较高水平的溶血磷脂酰胆碱(18:1)和 GM3 d18:1/20:0 显示 AD 进展率分别高 19%和 17%(Wald 检验:P=3.9×10-4 和 4.3×10-4)。棕榈油酸酰胺、油酰胺、二酰基甘油和醚脂也被确定为 pMCI 患者基线时明显改变的代谢物。代谢物和基因组学数据的综合分析表明,结合代谢物和基因型信息可提高 AD 进展的预测性能,这表明代谢组学对于补充基因组数据至关重要。总之,多组学数据的重新分析为检测 AD 病理学的早期发展并部分理解与年龄相关的 AD 发病机制中的代谢变化提供了新的见解。