title: Deciphering metabolic abnormalities associated with Alzheimer's disease in the APP/PS1 mouse model using integrated metabolomic approaches.
abstract: The transgenic mouse APP/PS1 is widely employed by neuroscientists because reproduces well some of the neuropathological and cognitive deficits observed in human Alzheimer's disease. In this study, serum samples from APP/PS1 mice (n = 30) and wild-type controls (n = 30) were analyzed using a metabolomic multiplatform based on the combination of gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry, in order to obtain wide information about serum metabolome. Metabolic profiles showed significant differences between the groups of study, and numerous metabolites were identified as potential players in the development of Alzheimer-type disorders in this transgenic model. Pathway analysis revealed the involvement of multiple metabolic networks in the underlying pathology, such as deficiencies in energy metabolism, altered amino acid homeostasis, abnormal membrane lipid metabolism, and other impairments related to the integrity of the central nervous system. It is noteworthy that some of these metabolomic markers are in accordance with pathological alterations observed in human Alzheimer's disease, while others have not been previously described. Therefore, these results demonstrate the potential of metabolomics and the use of transgenic animal models to understand the pathogenesis of Alzheimer's disease.
authors.affiliation: 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.forename: Raúl
authors.initials: R
authors.lastname: González-Domínguez
authors.affiliation: 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.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.
authors.forename: Javier
authors.initials: J
authors.lastname: Vitorica
authors.affiliation: 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.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Ariza
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D055432:Metabolomics; D051379:Mice; D008822:Mice, Transgenic; D015999:Multivariate Analysis; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D053764:Presenilin-1
keywords: APP/PS1 mice; Alzheimer's disease; Metabolomics; Serum