González-Domínguez Raúl, García Antonia, García-Barrera Tamara, Barbas Coral, Gómez-Ariza José Luis
Department of Chemistry and CC.MM, Faculty of Experimental Science, University of Huelva, Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Huelva, Spain.
Electrophoresis. 2014 Dec;35(23):3321-30. doi: 10.1002/elps.201400196. Epub 2014 Oct 9.
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.
人们对发现阿尔茨海默病的早期诊断生物标志物有着浓厚兴趣，代谢组学在这方面展现出巨大潜力。在这项工作中，一种基于超滤和毛细管电泳-质谱分析的代谢组学方法被用于获取血清样本中极性代谢物的代表性指纹图谱，以便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，能够根据疾病阶段对患者进行分类，进而识别潜在标志物。随着疾病进展，观察到胆碱、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-苯丙氨酸以及不同的中链酰基肉碱水平显著升高。另一方面，这些血清样本中的天冬酰胺、蛋氨酸、组氨酸、肉碱、乙酰亚精胺和C5-肉碱含量降低。通过这种方式，发现多个重要途径与潜在病理过程相关，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。
