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Altered Brain Metabolome Is Associated with Memory Impairment in the rTg4510 Mouse Model of Tauopathy

1
Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX 75226, USA
2
Servei de Bioquímica, Laboratori Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
3
Research Institute, Hospital de la Santa Creu i Sant Pau and CIBERDEM, Institute of Health Carlos III, 08041 Barcelona, Spain
4
Institute of Biomedical Research of Barcelona (IIBB)—Spanish National Research Council (CSIC), Biomedical Research Institute Sant Pau (IIB Sant Pau) and CIBERCV, Institute of Health Carlos III, 08036 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(2), 69; https://doi.org/10.3390/metabo10020069 (registering DOI)
Received: 23 December 2019 / Revised: 1 February 2020 / Accepted: 5 February 2020 / Published: 14 February 2020
Alzheimer’s disease (AD) is characterized, amongst other features, by the pathologic accumulation of abnormally phosphorylated tau filaments in neurons that lead to neurofibrillary tangles. However, the molecular mechanisms by which the abnormal processing of tau leads to neurodegeneration and cognitive impairment remain unknown. Metabolomic techniques can comprehensively assess disturbances in metabolic pathways that reflect changes downstream from genomic, transcriptomic and proteomic systems. In the present study, we undertook a targeted metabolomic approach to determine a total of 187 prenominated metabolites in brain cortex tissue from wild type and rTg4510 animals (a mice model of tauopathy), in order to establish the association of metabolic pathways with cognitive impairment. This targeted metabolomic approach revealed significant differences in metabolite concentrations of transgenic mice. Brain glutamine, serotonin and sphingomyelin C18:0 were found to be predictors of memory impairment. These findings provide informative data for future research on AD, since some of them agree with pathological alterations observed in diseased humans. View Full-Text
Keywords: metabolomics; Alzheimer’s disease; tauopathy; rTg4510 mice; cognitive impairment metabolomics; Alzheimer’s disease; tauopathy; rTg4510 mice; cognitive impairment
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Tondo, M.; Wasek, B.; Escola-Gil, J.C.; de Gonzalo-Calvo, D.; Harmon, C.; Arning, E.; Bottiglieri, T. Altered Brain Metabolome Is Associated with Memory Impairment in the rTg4510 Mouse Model of Tauopathy. Metabolites 2020, 10, 69.

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