RT Journal Article
T1 Region-specific metabolic alterations in the brain of the APP/PS1 transgenic mice of Alzheimer's disease
A1 González Domínguez, Raúl
A1 García Barrera, Tamara
A1 Vitorica Ferrández, Javier
A1 Gómez Ariza, José Luis
AB 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.
PB Elsevier
SN 0925-4439
YR 2014
FD 2014
LK http://hdl.handle.net/10272/14477
UL http://hdl.handle.net/10272/14477
LA eng
NO González Domínguez, R., García Barrera, T., Vitorica Ferrández, J., Gómez Ariza, J.L.: "Region-specific metabolic alterations in the brain of the APP/PS1 transgenic mice of Alzheimer's disease", Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1842, n. 12, Part A, págs.2395-2402, (2014). DOI: 10.1016/j.bbadis.2014.09.014.
NO This work was supported by the projects CTM2012-38720-C03-01 from the Ministerio de Ciencia e Innovacion and P012-FQM-0442 and P009-FQM-4659 from the Consejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia). Raul Gonzalez Dominguez thanks the Ministerio de Educacion (AP2010-4278) for a predoctoral scholarship.
DS Repositorio Institucional de la Universidad de Huelva
RD 1 jun 2026