Journal
ELECTROPHORESIS
Volume 35, Issue 23, Pages 3321-3330Publisher
WILEY
DOI: 10.1002/elps.201400196
Keywords
Alzheimer's disease; CE-MS; Metabolomics; Mild cognitive impairment
Funding
- Ministerio de Ciencia e Innovacion [CTM2012-38720-C03-01]
- MCIT from Ministero de Economia y Competitividad [CTQ2011-23562]
- Consejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia) [P012-FQM-0442, P009-FQM-4659]
- Ministerio de Educacion
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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.
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