Altered Expression of Human Mitochondrial Branched Chain Aminotransferase in Dementia with Lewy Bodies and Vascular Dementia

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dc.contributor.authorAshby, Emma L.en
dc.contributor.authorKierzkowska, Martaen
dc.contributor.authorHull, Jonathonen
dc.contributor.authorKehoe, Patrick G.en
dc.contributor.authorHutson, Susan M.en
dc.contributor.authorConway, Myra E.en
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2019-10-08T19:18:11Zen
dc.date.available2019-10-08T19:18:11Zen
dc.date.issued2017-01en
dc.description.abstractCytosolic and mitochondrial human branched chain aminotransferase (hBCATc and hBCATm, respectively) play an integral role in brain glutamate metabolism. Regional increased levels of hBCATc in the CA1 and CA4 region of Alzheimer's disease (AD) brain together with increased levels of hBCATm in frontal and temporal cortex of AD brains, suggest a role for these proteins in glutamate excitotoxicity. Glutamate toxicity is a key pathogenic feature of several neurological disorders including epilepsy associated dementia, AD, vascular dementia (VaD) and dementia with Lewy bodies (DLB). To further understand if these increases are specific to AD, the expression profiles of hBCATc and hBCATm were examined in other forms of dementia including DLB and VaD. Similar to AD, levels of hBCATm were significantly increased in the frontal and temporal cortex of VaD cases and in frontal cortex of DLB cases compared to controls, however there were no observed differences in hBCATc between groups in these areas. Moreover, multiple forms of hBCATm were observed that were particular to the disease state relative to matched controls. Real-time PCR revealed similar expression of hBCATm mRNA in frontal and temporal cortex for all cohort comparisons, whereas hBCATc mRNA expression was significantly increased in VaD cases compared to controls. Collectively our results suggest that hBCATm protein expression is significantly increased in the brains of DLB and VaD cases, similar to those reported in AD brain. These findings indicate a more global response to altered glutamate metabolism and suggest common metabolic responses that might reflect shared neurodegenerative mechanisms across several forms of dementia.en
dc.description.notesThis work was supported by Alzheimer's Research Trust, UK (ARUK). The SWDBB, which provided the tissue and clinical data for this study, is supported by BRACE (Bristol Research into Alzheimer's and Care of the Elderly), Brains for Dementia Research and the Medical Research Council. We would like to also acknowledge the valuable academic input from Prof Seth Love, University of Bristol, UK.en
dc.description.sponsorshipAlzheimer's Research Trust, UK (ARUK); BRACE (Bristol Research into Alzheimer's and Care of the Elderly); Brains for Dementia Research; Medical Research Councilen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1007/s11064-016-1855-7en
dc.identifier.eissn1573-6903en
dc.identifier.issn0364-3190en
dc.identifier.issue1en
dc.identifier.pmid26980008en
dc.identifier.urihttp://hdl.handle.net/10919/94411en
dc.identifier.volume42en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBranched chain aminotransferaseen
dc.subjecthBCATmen
dc.subjecthBCATcen
dc.subjectGlutamateen
dc.subjectAlzheimer's diseaseen
dc.subjectVascular dementiaen
dc.subjectDementia with Lewy bodyen
dc.titleAltered Expression of Human Mitochondrial Branched Chain Aminotransferase in Dementia with Lewy Bodies and Vascular Dementiaen
dc.title.serialNeurochemical Researchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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