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dc.contributor.authorPaglia G
dc.contributor.authorStocchero M
dc.contributor.authorCacciatore S
dc.contributor.authorLai S
dc.contributor.authorAngel P
dc.contributor.authorAlam MT
dc.contributor.authorKeller M
dc.contributor.authorRalser M
dc.contributor.authorAstarita G
dc.date.accessioned2018-09-25T14:52:13Z
dc.date.available2018-09-25T14:52:13Z
dc.date.issued2016
dc.identifier.issn1535-3893
dc.identifier.urihttp://dx.doi.org/10.1021/acs.jproteome.5b01020
dc.identifier.urihttp://hdl.handle.net/10863/6104
dc.description.abstractAlzheimer's disease (AD) is the most common cause of adult dementia. Yet the complete set of molecular changes accompanying this inexorable, neurodegenerative disease remains elusive. Here we adopted an unbiased lipidomics and metabolomics approach to surveying frozen frontal cortex samples from clinically characterized AD patients (n = 21) and age-matched controls (n = 19), revealing marked molecular differences between them. Then, by means of metabolomic pathway analysis, we incorporated the novel molecular information into the known biochemical pathways and compared it with the results of a metabolomics meta-analysis of previously published AD research. We found six metabolic pathways of the central metabolism as well as glycerophospholipid metabolism predominantly altered in AD brains. Using targeted metabolomics approaches and MS imaging, we confirmed a marked dysregulation of mitochondrial aspartate metabolism. The altered metabolic pathways were further integrated with clinical data, showing various degrees of correlation with parameters of dementia and AD pathology. Our study highlights specific, altered biochemical pathways in the brains of individuals with AD compared with those of control subjects, emphasizing dysregulation of mitochondrial aspartate metabolism and supporting future venues of investigation.en_US
dc.language.isoenen_US
dc.rights
dc.titleUnbiased metabolomic investigation of Alzheimer’s disease brain points to dysregulation of mitochondrial aspartate metabolismen_US
dc.typeArticleen_US
dc.date.updated2018-09-25T14:22:29Z
dc.language.isiEN-GB
dc.journal.titleJournal of Proteome Research
dc.description.fulltextnoneen_US


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