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Using direct infusion mass spectrometry for serum metabolomics in Alzheimer’s disease

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Abstract

Currently, there is no cure for Alzheimer’s disease and early diagnosis is very difficult, since no biomarkers have been established with the necessary reliability and specificity. For the discovery of new biomarkers, the application of omics is emerging, especially metabolomics based on the use of mass spectrometry. In this work, an analytical approach based on direct infusion electrospray mass spectrometry was applied for the first time to blood serum samples in order to elucidate discriminant metabolites. Complementary methodologies of extraction and mass spectrometry analysis were employed for comprehensive metabolic fingerprinting. Finally, the application of multivariate statistical tools allowed us to discriminate Alzheimer patients and healthy controls, and identify some compounds as potential markers of disease. This approach provided a global vision of disease, given that some important metabolic pathways could be studied, such as membrane destabilization processes, oxidative stress, hypometabolism, or neurotransmission alterations. Most remarkable results are the high levels of phospholipids containing saturated fatty acids, respectively, polyunsaturated ones and the high concentration of whole free fatty acids in Alzheimer’s serum samples. Thus, these results represent an interesting approximation to understand the pathogenesis of disease and the identification of potential biomarkers.

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Abbreviations

AD:

Alzheimer’s disease

AUC:

Area under the curve

Ch:

Choline

CV:

Coefficient of variation

DHA:

Docosahexaenoic acid

DIMS:

Direct infusion mass spectrometry

ESI:

Electrospray ionization

FC:

Fold change

FFA:

Free fatty acid

GPCh:

Glycerophosphocholine

HC:

Healthy control

LPC:

Lyso-phosphatidylcholine

MS:

Mass spectrometry

MS/MS:

Tandem mass spectrometry

PC:

Phosphatidylcholine

PLS-DA:

Partial least squares discriminant analysis

PPC:

Choline plasmalogen

PPE:

Ethanolamine plasmalogen

PUFA:

Polyunsaturated fatty acid

ROC:

Receiving operating characteristic

SFA:

Saturated fatty acid

TG:

Triglyceride

VIP:

Variable importance in the projection

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Acknowledgments

This work was supported by the projects CTM2012-38720-C03-01 from the Ministerio de Ciencia e Innovación and P008-FQM-3554 and P009-FQM-4659 from the Consejería de Innovación, Ciencia y Empresa (Junta de Andalucía). Raúl González Domínguez thanks the Ministerio de Educación for a predoctoral scholarship. The authors also thank to Dr. Alberto Blanco and Carlos Salgado from Hospital Juan Ramón Jiménez for providing serum samples.

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Authors and Affiliations

  1. Department of Chemistry and CC.MM, Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain

    R. González-Domínguez, T. García-Barrera & J. L. Gómez-Ariza

  2. Campus of Excellence International ceiA3, University of Huelva, Campus de El Carmen, 21007, Huelva, Spain

    R. González-Domínguez, T. García-Barrera & J. L. Gómez-Ariza

  3. Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007, Huelva, Spain

    R. González-Domínguez, T. García-Barrera & J. L. Gómez-Ariza

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  1. R. González-Domínguez
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  2. T. García-Barrera
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  3. J. L. Gómez-Ariza
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Correspondence to T. García-Barrera or J. L. Gómez-Ariza.

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González-Domínguez, R., García-Barrera, T. & Gómez-Ariza, J.L. Using direct infusion mass spectrometry for serum metabolomics in Alzheimer’s disease. Anal Bioanal Chem 406, 7137–7148 (2014). https://doi.org/10.1007/s00216-014-8102-3

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