Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder

Show simple item record Xu, J en Begley, P en Church, SJ en Patassini, S en Hollywood, KA en Jüllig, M en Curtis, Maurice en Waldvogel, Henry en Faull, Richard en Unwin, RD en Cooper, Garth en 2016-07-26T05:29:25Z en 2016-06 en
dc.identifier.citation Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2016, 1862 (6), pp. 1084 - 1092 en
dc.identifier.issn 0925-4439 en
dc.identifier.uri en
dc.description.abstract Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. en
dc.description.uri en
dc.publisher Elsevier en
dc.relation.ispartofseries Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
dc.rights.uri en
dc.rights.uri en
dc.title Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.bbadis.2016.03.001 en
pubs.issue 6 en
pubs.begin-page 1084 en
pubs.volume 1862 en
dc.description.version VoR – Version of Record en
dc.rights.holder Copyright: The Authors en
dc.identifier.pmid 26957286 en en
pubs.end-page 1092 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 524592 en Medical and Health Sciences en Medical Sciences en Anatomy and Medical Imaging en Science en Biological Sciences en Science Research en Maurice Wilkins Centre (2010-2014) en
pubs.record-created-at-source-date 2016-07-26 en
pubs.dimensions-id 26957286 en

Files in this item

Find Full text

This item appears in the following Collection(s)

Show simple item record


Search ResearchSpace