RT Journal Article
T1 Metabolomic investigation of systemic manifestations associated with Alzheimer's disease in the APP/PS1 transgenic mouse model
A1 González Domínguez, Raúl
A1 García Barrera, Tamara
A1 Vitorica, Javier
A1 Gómez Ariza, José Luis
AB There is growing evidence that Alzheimer's disease may be a widespread systemic disorder, so peripheral organs could be affected by pathological mechanisms occurring in this neurodegenerative disease. For this reason, a double metabolomic platform based on the combination of gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry was used for the first time to investigate metabolic changes in liver and kidney from the transgenic mice APP/PS1 against wild-type controls. Multivariate statistics showed significant differences in levels of numerous metabolites including phospholipids, sphingolipids, acylcarnitines, steroids, amino acids and other compounds, which denotes that multiple pathways might be associated with systemic pathogenesis of Alzheimer's in this mouse model, such as bioenergetic failures, oxidative stress, altered metabolism of membrane lipids, hyperammonemia or impaired homeostasis of steroids. Furthermore, it is noteworthy that some novel pathological mechanisms were found, such as impaired gluconeogenesis, polyol pathway or metabolism of branched chain amino acids, not previously described for Alzheimer's disease. Therefore, these findings clearly support the hypothesis that Alzheimer's disease may be considered as a systemic disorder.
PB Royal Society of Chemistry
SN 1742-206X
SN 1742-2051 (electrónico)
YR 2015
FD 2015
LK http://hdl.handle.net/10272/14677
UL http://hdl.handle.net/10272/14677
LA eng
NO González Domínguez, R., García Barrera, T., Vitorica, J., Gómez Ariza, J.L.: "Metabolomic investigation of systemic manifestations associated with Alzheimer's disease in the APP/PS1 transgenic mouse model". Molecular BioSystems. Vol. 11, n. 9, págs. 2429-2440, (2015). DOI: 10.1039/C4MB00747F
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 for a predoctoral scholarship (AP2010-4278).
DS Repositorio Institucional de la Universidad de Huelva
RD 31 may 2026