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

• Published in: PloS one Vol. 13; no. 3; p. e0191815
• Main Authors: Wood, Paul L, Tippireddy, Soumya, Feriante, Joshua, Woltjer, Randall L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-03-2018; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Biology and Life Sciences; Biomarkers - blood; Biomarkers - metabolism; Care and treatment; Development and progression; Diglycerides - blood; Diglycerides - metabolism; Female; Frontal Lobe - metabolism; Frontal Lobe - pathology; Humans; Lewy body disease; Lewy Body Disease - blood; Lewy Body Disease - metabolism; Male; Medical examination; Medicine and Health Sciences; Middle Aged; Neocortex - metabolism; Neocortex - pathology; Neurodegenerative Diseases - blood; Neurodegenerative Diseases - metabolism; Parkinson disease; Parkinson Disease - blood; Parkinson Disease - metabolism; Prefrontal cortex
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0191815

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.
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.
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.