Metabolomic profiling of serum in the progression of Alzheimer's disease by capillary electrophoresis-mass spectrometry
Metabolomic profiling of serum in the progression of Alzheimer's disease by capillary electrophoresis-mass spectrometry
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DOI：
10.1002/elps.201400196
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发表时间：
2014-12-01
期刊：
影响因子：
2.9
通讯作者：
Luis Gomez-Ariza, Jose
中科院分区：
文献类型：
--
作者：
Gonzalez-Dominguez, Raul;Garcia, Antonia;Luis Gomez-Ariza, Jose
人们对阿尔茨海默氏病早期诊断生物标志物的发现非常感兴趣，代谢组学在这方面表现出巨大的潜力。在这项工作中，基于超滤和 CE-MS 分析的代谢组学方法已被用于从血清样本中获得极性代谢物的代表性指纹，以区分阿尔茨海默病患者、轻度认知障碍患者和健康对照。通过使用偏最小二乘判别分析，可以根据疾病阶段对患者进行分类，然后识别潜在的标志物。随着疾病的进展，胆碱、肌酐、不对称二甲基精氨酸、同型半胱氨酸-半胱氨酸二硫化物、苯丙氨酰-苯丙氨酸和不同中链酰基肉碱的水平显着增加。另一方面，这些血清样品中的天冬酰胺、蛋氨酸、组氨酸、肉碱、乙酰亚精胺和C5-肉碱有所减少。通过这种方式，发现了与潜在病理学有关的多种重要途径，例如氧化应激或能量代谢缺陷。然而，最有趣的结果与几种血管危险因素与阿尔茨海默病的关联有关。
There is high interest in the discovery of early diagnostic biomarkers of Alzheimer's disease, for which metabolomics exhibits a great potential. In this work, a metabolomic approach based on ultrafiltration and analysis by CE-MS has been used to obtain representative fingerprints of polar metabolites from serum samples in order to distinguish between patients with Alzheimer's disease, mild cognitive impairment, and healthy controls. By the use of partial least squares discriminant analysis it was possible to classify patients according to the disease stage and then identify potential markers. Significant increase was observed with progression of disease in levels of choline, creatinine, asymmetric dimethyl-arginine, homocysteine-cysteine disulfide, phenylalanyl-phenylalanine, and different medium chain acylcarnitines. On the other hand, asparagine, methionine, histidine, carnitine, acetyl-spermidine, and C5-carnitine were reduced in these serum samples. In this way, multiple essential pathways were found implicated in the underlying pathology, such as oxidative stress or defects in energy metabolism. However, the most interesting results are related to the association of several vascular risk factors with Alzheimer's disease.