期刊
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
卷 102, 期 -, 页码 425-435出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2014.10.009
关键词
Metabolomics; APP/PS1 mice; Brain regions; Direct infusion mass spectrometry; Alzheimer's disease
资金
- Ministerio de Ciencia e Innovacion [CTM2012-38720-C03-01]
- Consejeria de Innovacion, Ciencia y Empresa (Junta de Andalucia) [P008-FQM-3554, P009-FQM-4659]
- Ministerio de Educacion
The identification of pathological mechanisms underlying to Alzheimer's disease is of great importance for the discovery of potential markers for diagnosis and disease monitoring. In this study, we investigated regional metabolic alterations in brain from the APP/PS1 mice, a transgenic model that reproduces well some of the neuropathological and cognitive deficits observed in human Alzheimer's disease. For this purpose, hippocampus, cortex, cerebellum and olfactory bulbs were analyzed using a high-throughput metabolomic approach based on direct infusion mass spectrometry. Metabolic fingerprints showed significant differences between transgenic and wild-type mice in all brain tissues, being hippocampus and cortex the most affected regions. Alterations in numerous metabolites were detected including phospholipids, fatty acids, purine and pyrimidine metabolites, acylcarnitines, sterols and amino acids, among others. Furthermore, metabolic pathway analysis revealed important alterations in homeostasis of lipids, energy management, and metabolism of amino acids and nucleotides. Therefore, these findings demonstrate the potential of metabolomic screening and the use of transgenic models for understanding pathogenesis of Alzheimer's disease. (C) 2014 Elsevier B.V. All rights reserved.
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