Metabolomic changes in autopsy-confirmed Alzheimer's disease.
Metabolomic changes in autopsy-confirmed Alzheimer's disease.
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DOI：
10.1016/j.jalz.2010.06.001
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Welsh-Bohmer KA
中科院分区：
文献类型：
--
作者：
Kaddurah-Daouk R;Rozen S;Matson W;Han X;Hulette CM;Burke JR;Doraiswamy PM;Welsh-Bohmer KA
代谢组学是全球性的生物化学科学，它提供了强大的工具来描绘代谢网络中的扰动，并使大量代谢物能够同时量化，以识别可能为疾病提供洞察力的代谢扰动。在这项初步研究中，我们采用了一种有针对性的基于电化学的代谢组学方法，在此方法中，液相色谱和库仑阵列检测可以对关键神经递质途径(多巴胺和5-羟色胺)和参与氧化应激的途径中的30多种代谢物进行定量。利用尸检确诊的15例AD和15例非痴呆患者的脑室脑脊液(CSF)样本，采用回归模型、相关性、Wilcoxon秩和检验和t检验，我们确定了AD患者的酪氨酸、色氨酸、嘌呤和生育酚通路的改变。去甲肾上腺素及其相关代谢物的减少也被观察到，这与先前的文献一致。这些数据支持在更大的临床AD样本以及临床前疾病中作为生物标志物的代谢组学的进一步研究。
Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of a large number of metabolites to identify metabolic perturbances that might provide insights into disease. In this pilot study we take a targeted electrochemistry based metabolomics approach where liquid chromatography followed by coulometric array detection enables quantification of over thirty metabolites within key neurotransmitter pathways (dopamine and serotonin) and pathways involved in oxidative stress. Using samples from post-mortem ventricular cerebrospinal fluid (CSF) (15 AD and 15 non-demented subjects with autopsy confirmed diagnoses) and using regression models, correlations, Wilcoxon rank-sum tests and t-tests we identified alterations in tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD. Reductions in norepinephrine and its related metabolites were also seen, consistent with prior literature. These data support further investigation of metabolomics in larger samples of clinical AD as well as in those with preclinical disease for utility as biomarkers.
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