title: Region-specific metabolic alterations in the brain of the APP/PS1 transgenic mice of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide, but its etiology is still not completely understood. The identification of underlying pathological mechanisms is becoming increasingly important for the discovery of biomarkers and therapies, for which metabolomics presents a great potential. In this work, we studied metabolic alterations in different brain regions of the APP/PS1 mice by using a high-throughput metabolomic approach based on the combination of gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry. Multivariate statistics showed that metabolomic perturbations are widespread, affecting mainly the hippocampus and the cortex, but are also present in regions not primarily associated with AD such as the striatum, cerebellum and olfactory bulbs. Multiple metabolic pathways could be linked to the development of AD-type disorders in this mouse model, including abnormal purine metabolism, bioenergetic failures, dyshomeostasis of amino acids and disturbances in membrane lipids, among others. Interestingly, region-specific alterations were observed for some of the potential markers identified, associated with abnormal fatty acid composition of phospholipids and sphingomyelins, or differential regulation of neurotransmitter amino acids (e.g. glutamate, glycine, serine, N-acetyl-aspartate), not previously described to our knowledge. Therefore, these findings could provide a new insight into brain pathology in Alzheimer's disease.
authors.affiliation: Department of Chemistry, 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: raul.gonzalez@dqcm.uhu.es.
authors.forename: Raúl
authors.initials: R
authors.lastname: González-Domínguez
authors.affiliation: Department of Chemistry, 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.garcia@dqcm.uhu.es.
authors.forename: Tamara
authors.initials: T
authors.lastname: García-Barrera
authors.affiliation: 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. Electronic address: vitorica@us.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Vitorica
authors.affiliation: Department of Chemistry, 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.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Ariza
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055432:Metabolomics / Q000379:methods; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D009154:Mutation; D017072:Neostriatum / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: APP/PS1 mouse; Alzheimer's disease; Metabolomics; Pathology; Region-specific alteration