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Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease

BACKGROUND: Research from our laboratory, and that of other investigators, has demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of subjects with Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). We have extended these observations to investigate the...

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Autores principales: Wood, Paul L., Tippireddy, Soumya, Feriante, Joshua, Woltjer, Randall L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841652/
https://www.ncbi.nlm.nih.gov/pubmed/29513680
http://dx.doi.org/10.1371/journal.pone.0191815
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author Wood, Paul L.
Tippireddy, Soumya
Feriante, Joshua
Woltjer, Randall L.
author_facet Wood, Paul L.
Tippireddy, Soumya
Feriante, Joshua
Woltjer, Randall L.
author_sort Wood, Paul L.
collection PubMed
description BACKGROUND: Research from our laboratory, and that of other investigators, has demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of subjects with Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). We have extended these observations to investigate the frontal cortex of subjects with Parkinson’s disease (PD) and Lewy Body Disease (LBD), with and without coexisting pathologic features of AD. METHODS/PRINCIPAL FINDINGS: Utilizing a high-resolution mass spectrometry analytical platform, we clearly demonstrate that DAG levels are significantly increased in the frontal cortex of subjects with PD, LBD with intermediate neocortical AD neuropathology, and in LBD with established neocortical AD neuropathology. In the case of the PD cohort, increases in cortical DAG levels were detected in cases with no neocortical pathology but were greater in subjects with neocortical pathology. These data suggest that DAG changes occur early in the disease processes and are amplified as cortical dysfunction becomes more established. CONCLUSIONS: These findings suggest that altered DAG synthesis/metabolism is a common feature of neurodegenerative diseases, characterized by proteinopathy, that ultimately result in cognitive deficits. With regard to the mechanism responsible for these biochemical alterations, selective decrements in cortical levels of phosphatidylcholines in LBD and PD suggest that augmented degradation and/or decreased synthesis of these structural glycerophospholipids may contribute to increases in the pool size of free DAGs. The observed augmentation of DAG levels may be phospholipase-driven since neuroinflammation is a consistent feature of all disease cohorts. If this conclusion can be validated it would support utilizing DAG levels as a biomarker of the early disease process and the investigation of early intervention with anti-inflammatory agents.
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spelling pubmed-58416522018-03-23 Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease Wood, Paul L. Tippireddy, Soumya Feriante, Joshua Woltjer, Randall L. PLoS One Research Article BACKGROUND: Research from our laboratory, and that of other investigators, has demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of subjects with Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). We have extended these observations to investigate the frontal cortex of subjects with Parkinson’s disease (PD) and Lewy Body Disease (LBD), with and without coexisting pathologic features of AD. METHODS/PRINCIPAL FINDINGS: Utilizing a high-resolution mass spectrometry analytical platform, we clearly demonstrate that DAG levels are significantly increased in the frontal cortex of subjects with PD, LBD with intermediate neocortical AD neuropathology, and in LBD with established neocortical AD neuropathology. In the case of the PD cohort, increases in cortical DAG levels were detected in cases with no neocortical pathology but were greater in subjects with neocortical pathology. These data suggest that DAG changes occur early in the disease processes and are amplified as cortical dysfunction becomes more established. CONCLUSIONS: These findings suggest that altered DAG synthesis/metabolism is a common feature of neurodegenerative diseases, characterized by proteinopathy, that ultimately result in cognitive deficits. With regard to the mechanism responsible for these biochemical alterations, selective decrements in cortical levels of phosphatidylcholines in LBD and PD suggest that augmented degradation and/or decreased synthesis of these structural glycerophospholipids may contribute to increases in the pool size of free DAGs. The observed augmentation of DAG levels may be phospholipase-driven since neuroinflammation is a consistent feature of all disease cohorts. If this conclusion can be validated it would support utilizing DAG levels as a biomarker of the early disease process and the investigation of early intervention with anti-inflammatory agents. Public Library of Science 2018-03-07 /pmc/articles/PMC5841652/ /pubmed/29513680 http://dx.doi.org/10.1371/journal.pone.0191815 Text en © 2018 Wood et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wood, Paul L.
Tippireddy, Soumya
Feriante, Joshua
Woltjer, Randall L.
Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease
title Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease
title_full Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease
title_fullStr Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease
title_full_unstemmed Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease
title_short Augmented frontal cortex diacylglycerol levels in Parkinson’s disease and Lewy Body Disease
title_sort augmented frontal cortex diacylglycerol levels in parkinson’s disease and lewy body disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841652/
https://www.ncbi.nlm.nih.gov/pubmed/29513680
http://dx.doi.org/10.1371/journal.pone.0191815
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