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...

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Main Authors: Paul L Wood, Soumya Tippireddy, Joshua Feriante, Randall L Woltjer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5841652?pdf=render
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spelling doaj-394aa43bdd2549e5a4f8d53f4c249dba2020-11-25T02:01:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019181510.1371/journal.pone.0191815Augmented frontal cortex diacylglycerol levels in Parkinson's disease and Lewy Body Disease.Paul L WoodSoumya TippireddyJoshua FerianteRandall L WoltjerBACKGROUND: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.http://europepmc.org/articles/PMC5841652?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Paul L Wood
Soumya Tippireddy
Joshua Feriante
Randall L Woltjer
spellingShingle Paul L Wood
Soumya Tippireddy
Joshua Feriante
Randall L Woltjer
Augmented frontal cortex diacylglycerol levels in Parkinson's disease and Lewy Body Disease.
PLoS ONE
author_facet Paul L Wood
Soumya Tippireddy
Joshua Feriante
Randall L Woltjer
author_sort Paul L Wood
title 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_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_sort augmented frontal cortex diacylglycerol levels in parkinson's disease and lewy body disease.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
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.
url http://europepmc.org/articles/PMC5841652?pdf=render
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