title: 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.
abstract: Metabolomic analysis of brain tissue from transgenic mouse models of Alzheimer's disease has demonstrated a great potential for the study of pathological mechanisms and the development of new therapies and biomarkers for diagnosis. However, in order to translate these investigations to the clinical practice it is necessary to corroborate these findings in peripheral samples. To this end, this work considers the application of a novel metabolomic platform based on the combination of a two-steps extraction procedure with complementary analysis by direct infusion electrospray mass spectrometry and flow infusion atmospheric pressure photoionization mass spectrometry for a holistic investigation of metabolic abnormalities in serum samples from APP/PS1 mice. A number of metabolites were found to be perturbed in this mouse model, including increased levels of di- and tri-acylglycerols, eicosanoids, inosine, choline and glycerophosphoethanolamine; reduced content of cholesteryl esters, free fatty acids, lysophosphocholines, amino acids, energy-related metabolites, phosphoethanolamine and urea, as well as abnormal distribution of phosphocholines depending on the fatty acid linked to the molecular moiety. This allowed the elucidation of possible pathways disturbed underlying to disease (abnormal homeostasis of phospholipids leading to membrane breakdown, energy-related failures, hyperammonemia and hyperlipidemia, among others), thus demonstrating the utility of peripheral samples to investigate pathology in the APP/PS1 model.
authors: Department of Chemistry and CC.MM. Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain.
authors: Raúl
authors: R
authors: González-Domínguez
authors: Department of Chemistry and CC.MM. Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain. Electronic address: tamara@dqcm.uhu.es.
authors: Tamara
authors: T
authors: García-Barrera
authors: Department Bioquímica, Bromatologia, Toxicología y Medicina Legal, Faculty of Pharmacy, University of Seville, 41012 Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 41013 Seville, Spain; Instituto de Biomedicina de Sevilla (IBiS)-Hospital Universitario Virgen del Rocío/CSIC/University of Seville, 41013 Seville, Spain.
authors: Javier
authors: J
authors: Vitorica
authors: Department of Chemistry and CC.MM. Faculty of Experimental Sciences, University of Huelva, Campus de El Carmen, 21007 Huelva, Spain; Campus of Excellence International ceiA3, University of Huelva, Spain; Research Center of Health and Environment (CYSMA), University of Huelva, Campus de El Carmen, 21007 Huelva, Spain. Electronic address: ariza@uhu.es.
authors: José Luis
authors: JL
authors: Gómez-Ariza
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001274:Atmospheric Pressure; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D053764:Presenilin-1 / Q000378:metabolism*; D044967:Serum / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010743:Phospholipids; D053764:Presenilin-1
keywords: APP/PS1 mice; Alzheimer's disease; DI-ESI-MS; FI-APPI-MS; Metabolomics