Plasma metabolite profiles of Alzheimer's disease and mild cognitive impairment.
Plasma metabolite profiles of Alzheimer's disease and mild cognitive impairment.
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DOI：
10.1021/pr5000895
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发表时间：
2014-04
影响因子：
4.4
通讯作者：
Gang Wang;Yi Zhou;Feng Huang;Huidong Tang;Xu-hua Xu-Xu-hua-Xu-2112693262;Jia-Jian Liu;Ying Wang;Yulei Deng;
中科院分区：
文献类型：
--
作者：
Gang Wang;Yi Zhou;Feng Huang;Huidong Tang;Xu-hua Xu-Xu-hua-Xu-2112693262;Jia-Jian Liu;Ying Wang;Yulei Deng;
先前的研究已经证明阿尔茨海默病（AD）患者样本中的代谢物发生了改变。然而，其中许多研究的样本量相对较小，代谢物相对有限。在这里，我们应用了一个综合的平台，使用超高效液相色谱-飞行时间质谱和气相色谱-飞行时间质谱分析血浆样品从AD患者，遗忘型轻度认知障碍（aMCI）患者，和正常对照。鉴定了由六种血浆代谢物（花生四烯酸、N，N-二甲基甘氨酸、胸腺嘧啶、谷氨酰胺、谷氨酸和胞苷）组成的生物标志物组以区分AD患者与正常对照。另一组5种血浆代谢物（胸腺嘧啶、花生四烯酸、2-氨基己二酸、N，N-二甲基甘氨酸和5，8-十四碳二烯酸）能够区分aMCI患者和对照受试者。两种生物标志物组与临床诊断具有良好的一致性。2组代谢物标志物均涉及脂肪酸代谢、一碳代谢、氨基酸代谢和核酸代谢。此外，在不同阶段的患者中，以及在服用抗胆碱酯酶药物和未服用抗胆碱酯酶药物的患者中，未发现代谢物发生变化。这些发现提供了一个全面的全球血浆代谢产物谱，并可能有助于早期诊断以及了解AD和aMCI的致病机制。
Previous studies have demonstrated altered metabolites in samples of Alzheimer's disease (AD) patients. However, the sample size from many of them is relatively small and the metabolites are relatively limited. Here we applied a comprehensive platform using ultraperformance liquid chromatography-time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to analyze plasma samples from AD patients, amnestic mild cognitive impairment (aMCI) patients, and normal controls. A biomarker panel consisting of six plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid, and cytidine) was identified to discriminate AD patients from normal control. Another panel of five plasma metabolites (thymine, arachidonic acid, 2-aminoadipic acid, N,N-dimethylglycine, and 5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects. Both biomarker panels had good agreements with clinical diagnosis. The 2 panels of metabolite markers were all involved in fatty acid metabolism, one-carbon metabolism, amino acid metabolism, and nucleic acid metabolism. Additionally, no altered metabolites were found among the patients at different stages, as well as among those on anticholinesterase medication and those without anticholinesterase medication. These findings provide a comprehensive global plasma metabolite profiling and may contribute to making early diagnosis as well as understanding the pathogenic mechanism of AD and aMCI.