Abstract
The integration of complementary analytical platforms is nowadays the most common strategy for comprehensive metabolomics analysis of complex biological systems. In this chapter, we describe methods and tips for the application of a mass spectrometry multi-platform in Alzheimer’s disease research, based on the combination of direct mass spectrometry and orthogonal hyphenated approaches, namely, reversed-phase ultrahigh-performance liquid chromatography and gas chromatography. These procedures have been optimized for the analysis of multiple biological samples from human patients and transgenic animal models, including blood serum, various brain regions (e.g., hippocampus, cortex, cerebellum, striatum, olfactory bulbs), and other peripheral organs (e.g., liver, kidney, spleen, thymus).
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References
Maccioni RB, Muñoz JP, Barbeito L (2001) The molecular bases of Alzheimer’s disease and other neurodegenerative disorders. Arch Med Res 32:367–381
González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2014) Characterization of metal profiles in serum during the progression of Alzheimer’s disease. Metallomics 9:292–300
Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P (2007) Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS–ADRDA criteria. Lancet Neurol 6:734–746
González-Domínguez R, Sayago A, Fernández-Recamales Á (2017) Metabolomics in Alzheimer’s disease: the need of complementary analytical platforms for the identification of biomarkers to unravel the underlying pathology. J Chromatogr B Analyt Technol Biomed Life Sci 1071:75–92
González-Domínguez R, González-Domínguez Á, Sayago A, González-Sanz JD, Lechuga-Sancho AM, Fernández-Recamales Á (2021) Mechanistic insights into Alzheimer’s disease unveiled through the investigation of disturbances in central metabolites and metabolic pathways. Biomedicine 9:298
González-Domínguez R, Sayago A, Fernández-Recamales Á (2018) High-throughput direct mass spectrometry-based metabolomics to characterize metabolite fingerprints associated with Alzheimer’s disease pathogenesis. Meta 8:52
González-Domínguez R, Jáuregui O, Queipo-Ortuño MI, Andrés-Lacueva C (2020) Characterization of the human exposome by a comprehensive and quantitative large-scale multianalyte metabolomics platform. Anal Chem 92:13767–13775
Dunn WB, Broadhurst DI, Atherton HJ, Goodacre R, Griffin JL (2011) Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem Soc Rev 40:387–426
Gonzalez-Dominguez A, Duran-Guerrero E, Fernandez-Recamales A, Lechuga-Sancho AM, Sayago A, Schwarz M, Segundo C, Gonzalez-Dominguez R (2017) An overview on the importance of combining complementary analytical platforms in metabolomic research. Curr Top Med Chem 17:3289–3295
González-Domínguez R, Sayago A, Fernández-Recamales A (2017) Direct infusion mass spectrometry for metabolomic phenotyping of diseases. Bioanalysis 9:131–148
González-Domínguez R, González-Domínguez Á, Segundo C, Schwarz M, Sayago A, Mateos RM, Durán-Guerrero E, Lechuga-Sancho AM, Fernández-Recamales Á (2019) High-throughput metabolomics based on direct mass spectrometry analysis in biomedical research. In: D’Alessandro A (ed) High-throughput metabolomics, Methods in molecular biology, vol 1978. Humana, New York, pp 27–38
Pasikanti KK, Ho PC, Chan EC (2008) Gas chromatography/mass spectrometry in metabolic profiling of biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci 871:202–211
González-Domínguez R, González-Domínguez Á, Sayago A, Fernández-Recamales Á (2021) State-of-the-art mass spectrometry-based approaches to explore the polar metabolome: Alzheimer’s disease as a case study. In: Ramautar R (ed) Advanced mass spectrometry-based analytical separation techniques for probing the polar metabolome. Royal Society of Chemistry, London, pp 219–241
Kuehnbaum NL, Britz-McKibbin P (2013) New advances in separation science for metabolomics: resolving chemical diversity in a post-genomic era. Chem Rev 113:2437–2468
González-Domínguez R, González-Domínguez Á, Sayago A, Fernández-Recamales Á (2018) Mass spectrometry-based metabolomic multiplatform for Alzheimer’s disease research. In: Perneczky R (ed) Biomarkers for Alzheimer’s disease drug development. Methods in molecular biology, vol 1750. Humana Press, New York, pp 125–137
González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2014) Using direct infusion mass spectrometry for serum metabolomics in Alzheimer’s disease. Anal Bioanal Chem 406:7137–7148
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2014) Region-specific metabolic alterations in the brain of the APP/PS1 transgenic mice of Alzheimer’s disease. Biochim Biophys Acta 1842:2395–2402
Gago-Tinoco A, González-Domínguez R, García-Barrera T, Blasco-Moreno J, Bebianno MJ, Gómez-Ariza JL (2014) Metabolic signatures associated with environmental pollution by metals in Doñana National Park using P. clarkii as bioindicator. Environ Sci Pollut Res Int 21:13315–13323
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2015) High throughput multi-organ metabolomics in the APP/PS1 mouse model of Alzheimer’s disease. Electrophoresis 36:2237–2249
Sangster T, Major H, Plumb R, Wilson AJ, Wilson ID (2006) A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysis. Analyst 131:1075–1078
González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2015) Metabolite profiling for the identification of altered metabolic pathways in Alzheimer’s disease. J Pharm Biomed Anal 107:75–81
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2015) Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer’s disease by direct infusion mass spectrometry. J Pharm Biomed Anal 102:425–435
González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2015) Application of a novel metabolomic approach based on atmospheric pressure photoionization mass spectrometry using flow injection analysis for the study of Alzheimer’s disease. Talanta 131:480–489
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2015) Application of metabolomics based on direct mass spectrometry analysis for the elucidation of altered metabolic pathways in serum from the APP/PS1 transgenic model of Alzheimer’s disease. J Pharm Biomed Anal 107:378–385
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2015) Deciphering metabolic abnormalities associated with Alzheimer’s disease in the APP/PS1 mouse model using integrated metabolomic approaches. Biochimie 110:119–128
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2015) Metabolomic investigation of systemic manifestations associated with Alzheimer’s disease in the APP/PS1 transgenic mouse model. Mol BioSyst 11:2429–2440
González-Domínguez R, García-Barrera T, Vitorica J, Gómez-Ariza JL (2015) Metabolomics reveals significant impairments in the immune system of the APP/PS1 transgenic mice of Alzheimer’s disease. Electrophoresis 36:577–587
González-Domínguez R, García A, García-Barrera T, Barbas C, Gómez-Ariza JL (2014) Metabolomic profiling of serum in the progression of Alzheimer’s disease by capillary electrophoresis-mass spectrometry. Electrophoresis 35:3321–3330
González-Domínguez R, Rupérez FJ, García-Barrera T, Barbas C, Gómez-Ariza JL (2016) Metabolomic-driven elucidation of pathological mechanisms associated with Alzheimer’s disease and mild cognitive impairment. Curr Alzheimer Res 13:641–653
González-Domínguez R, González-Domínguez Á, Sayago A, Fernández-Recamales Á (2020) Recommendations and best practices for standardizing the pre-analytical processing of blood and urine samples in metabolomics. Meta 10:229
González-Domínguez R, Castilla-Quintero R, García-Barrera T, Gómez-Ariza JL (2014) Development of a metabolomic approach based on urine samples and direct infusion mass spectrometry. Anal Biochem 465:20–27
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González-Domínguez, Á., Sayago, A., Fernández-Recamales, Á., González-Domínguez, R. (2024). Mass Spectrometry-Based Metabolomics Multi-platform for Alzheimer’s Disease Research. In: Perneczky, R. (eds) Biomarkers for Alzheimer’s Disease Drug Development. Methods in Molecular Biology, vol 2785. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3774-6_6
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DOI: https://doi.org/10.1007/978-1-0716-3774-6_6
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