Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor

Elena A. Ostrakhovitch; Eun Suk Song; Jessica K.A. Macedo; Matthew S. Gentry; Jorge E. Quintero; Craig van Horne; Tritia R. Yamasaki

doi:10.1016/j.neulet.2021.136428

Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor

Elena A. Ostrakhovitch, Eun Suk Song, Jessica K.A. Macedo, Matthew S. Gentry, Jorge E. Quintero, Craig van Horne, Tritia R. Yamasaki

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.

Original language	English
Article number	136428
Journal	Neuroscience Letters
Volume	769
DOIs	https://doi.org/10.1016/j.neulet.2021.136428
State	Published - Jan 19 2022

Bibliographical note

Funding Information:
This study was supported by the University of Kentucky College of Medicine’s Brain and Epilepsy Alliance for Metabolism Research and a CCTS KL2 award under NIH UL1TR001998 (T.R.Y). The research was also supported by the National Institute of Health (NIH) grants R35 NS116824 (M.S.G.). J.K.A.M. was supported by NIH/NCI training grant T32CA165990.

Funding Information:
The authors would like to express our deep appreciation to our patients at the University of Kentucky Neuroscience Institute for their participation in this study. We are also grateful to Dr. Ramon Sun of the Neuroscience Department for constructive comments.

Publisher Copyright:
© 2021

Keywords

Alpha-synuclein
Cerebrospinal fluid
Metabolomic analysis
Parkinson's disease
Plasma

ASJC Scopus subject areas

Neuroscience (all)

Access to Document

10.1016/j.neulet.2021.136428

Cite this

@article{75377485aaaf4b3b89cb6dc0c8649ceb,

title = "Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor",

abstract = "Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.",

keywords = "Alpha-synuclein, Cerebrospinal fluid, Metabolomic analysis, Parkinson's disease, Plasma",

author = "Ostrakhovitch, {Elena A.} and Song, {Eun Suk} and Macedo, {Jessica K.A.} and Gentry, {Matthew S.} and Quintero, {Jorge E.} and {van Horne}, Craig and Yamasaki, {Tritia R.}",

note = "Funding Information: This study was supported by the University of Kentucky College of Medicine{\textquoteright}s Brain and Epilepsy Alliance for Metabolism Research and a CCTS KL2 award under NIH UL1TR001998 (T.R.Y). The research was also supported by the National Institute of Health (NIH) grants R35 NS116824 (M.S.G.). J.K.A.M. was supported by NIH/NCI training grant T32CA165990. Funding Information: The authors would like to express our deep appreciation to our patients at the University of Kentucky Neuroscience Institute for their participation in this study. We are also grateful to Dr. Ramon Sun of the Neuroscience Department for constructive comments. Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = jan,

day = "19",

doi = "10.1016/j.neulet.2021.136428",

language = "English",

volume = "769",

}

TY - JOUR

T1 - Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor

AU - Ostrakhovitch, Elena A.

AU - Song, Eun Suk

AU - Macedo, Jessica K.A.

AU - Gentry, Matthew S.

AU - Quintero, Jorge E.

AU - van Horne, Craig

AU - Yamasaki, Tritia R.

N1 - Funding Information: This study was supported by the University of Kentucky College of Medicine’s Brain and Epilepsy Alliance for Metabolism Research and a CCTS KL2 award under NIH UL1TR001998 (T.R.Y). The research was also supported by the National Institute of Health (NIH) grants R35 NS116824 (M.S.G.). J.K.A.M. was supported by NIH/NCI training grant T32CA165990. Funding Information: The authors would like to express our deep appreciation to our patients at the University of Kentucky Neuroscience Institute for their participation in this study. We are also grateful to Dr. Ramon Sun of the Neuroscience Department for constructive comments. Publisher Copyright: © 2021

PY - 2022/1/19

Y1 - 2022/1/19

N2 - Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.

AB - Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism. Elevated α-synuclein levels in plasma and CSF distinguished PD from ET. The perturbed metabolic state in PD was associated with imbalance in the pentose phosphate pathway, deficits in energy production, and change in NADPH, NADH and nicotinamide phosphoribosyltransferase levels. This work demonstrates significant metabolic differences in plasma and CSF of PD and ET patients.

KW - Alpha-synuclein

KW - Cerebrospinal fluid

KW - Metabolomic analysis

KW - Parkinson's disease

KW - Plasma

UR - http://www.scopus.com/inward/record.url?scp=85122231910&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85122231910&partnerID=8YFLogxK

U2 - 10.1016/j.neulet.2021.136428

DO - 10.1016/j.neulet.2021.136428

M3 - Article

C2 - 34971771

AN - SCOPUS:85122231910

SN - 0304-3940

VL - 769

JO - Neuroscience Letters

JF - Neuroscience Letters

M1 - 136428

ER -

Analysis of circulating metabolites to differentiate Parkinson's disease and essential tremor

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this