Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study

Abstract Huntington’s Disease (HD) is a progressive, fatal neurodegenerative condition. While generally considered for its devastating neurological phenotype, disturbances in other organ systems and metabolic pathways outside the brain have attracted attention for possible relevance to HD pathology,...

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Main Authors: Andrew McGarry, John Gaughan, Cory Hackmyer, Jacqueline Lovett, Mohammed Khadeer, Hamza Shaikh, Basant Pradhan, Thomas N. Ferraro, Irving W. Wainer, Ruin Moaddel
Format: Article
Language:English
Published: Nature Publishing Group 2020-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-77526-9
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spelling doaj-5ae9c5e256a348519a3dd38699b08cf52020-12-08T10:14:15ZengNature Publishing GroupScientific Reports2045-23222020-11-0110111310.1038/s41598-020-77526-9Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot studyAndrew McGarry0John Gaughan1Cory Hackmyer2Jacqueline Lovett3Mohammed Khadeer4Hamza Shaikh5Basant Pradhan6Thomas N. Ferraro7Irving W. Wainer8Ruin Moaddel9Department of Neurology, Cooper University Hospital and Cooper Medical School of Rowan UniversityDepartment of Neurology, Cooper University Hospital and Cooper Medical School of Rowan UniversityDepartment of Neurology, Cooper University Hospital and Cooper Medical School of Rowan UniversityBiomedical Research Center, National Institute On Aging, National Institutes of HealthBiomedical Research Center, National Institute On Aging, National Institutes of HealthDepartment of Neurology, Cooper University Hospital and Cooper Medical School of Rowan UniversityDepartment of Neurology, Cooper University Hospital and Cooper Medical School of Rowan UniversityDepartment of Biomedical Sciences, Cooper Medical School of Rowan UniversityDepartment of Neurology, Cooper University Hospital and Cooper Medical School of Rowan UniversityBiomedical Research Center, National Institute On Aging, National Institutes of HealthAbstract Huntington’s Disease (HD) is a progressive, fatal neurodegenerative condition. While generally considered for its devastating neurological phenotype, disturbances in other organ systems and metabolic pathways outside the brain have attracted attention for possible relevance to HD pathology, potential as therapeutic targets, or use as biomarkers of progression. In addition, it is not established how metabolic changes in the HD brain correlate to progression across the full spectrum of early to late-stage disease. In this pilot study, we sought to explore the metabolic profile across manifest HD from early to advanced clinical staging through metabolomic analysis by mass spectrometry in plasma and cerebrospinal fluid (CSF). With disease progression, we observed nominally significant increases in plasma arginine, citrulline, and glycine, with decreases in total and d-serine, cholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins. In CSF, worsening disease was associated with nominally significant increases in NAD+, arginine, saturated long chain free fatty acids, diacylglycerides, triacylglycerides, and sphingomyelins. Notably, diacylglycerides and triacylglyceride species associated with clinical progression were different between plasma and CSF, suggesting different metabolic preferences for these compartments. Increasing NAD+ levels strongly correlating with disease progression was an unexpected finding. Our data suggest that defects in the urea cycle, glycine, and serine metabolism may be underrecognized in the progression HD pathology, and merit further study for possible therapeutic relevance.https://doi.org/10.1038/s41598-020-77526-9
collection DOAJ
language English
format Article
sources DOAJ
author Andrew McGarry
John Gaughan
Cory Hackmyer
Jacqueline Lovett
Mohammed Khadeer
Hamza Shaikh
Basant Pradhan
Thomas N. Ferraro
Irving W. Wainer
Ruin Moaddel
spellingShingle Andrew McGarry
John Gaughan
Cory Hackmyer
Jacqueline Lovett
Mohammed Khadeer
Hamza Shaikh
Basant Pradhan
Thomas N. Ferraro
Irving W. Wainer
Ruin Moaddel
Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study
Scientific Reports
author_facet Andrew McGarry
John Gaughan
Cory Hackmyer
Jacqueline Lovett
Mohammed Khadeer
Hamza Shaikh
Basant Pradhan
Thomas N. Ferraro
Irving W. Wainer
Ruin Moaddel
author_sort Andrew McGarry
title Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study
title_short Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study
title_full Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study
title_fullStr Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study
title_full_unstemmed Cross-sectional analysis of plasma and CSF metabolomic markers in Huntington’s disease for participants of varying functional disability: a pilot study
title_sort cross-sectional analysis of plasma and csf metabolomic markers in huntington’s disease for participants of varying functional disability: a pilot study
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2020-11-01
description Abstract Huntington’s Disease (HD) is a progressive, fatal neurodegenerative condition. While generally considered for its devastating neurological phenotype, disturbances in other organ systems and metabolic pathways outside the brain have attracted attention for possible relevance to HD pathology, potential as therapeutic targets, or use as biomarkers of progression. In addition, it is not established how metabolic changes in the HD brain correlate to progression across the full spectrum of early to late-stage disease. In this pilot study, we sought to explore the metabolic profile across manifest HD from early to advanced clinical staging through metabolomic analysis by mass spectrometry in plasma and cerebrospinal fluid (CSF). With disease progression, we observed nominally significant increases in plasma arginine, citrulline, and glycine, with decreases in total and d-serine, cholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, phosphatidylethanolamines, and sphingomyelins. In CSF, worsening disease was associated with nominally significant increases in NAD+, arginine, saturated long chain free fatty acids, diacylglycerides, triacylglycerides, and sphingomyelins. Notably, diacylglycerides and triacylglyceride species associated with clinical progression were different between plasma and CSF, suggesting different metabolic preferences for these compartments. Increasing NAD+ levels strongly correlating with disease progression was an unexpected finding. Our data suggest that defects in the urea cycle, glycine, and serine metabolism may be underrecognized in the progression HD pathology, and merit further study for possible therapeutic relevance.
url https://doi.org/10.1038/s41598-020-77526-9
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