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Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease
Author(s) -
Kremer Thomas,
Taylor Kirsten I.,
SiebourgPolster Juliane,
Gerken Thomas,
Staempfli Andreas,
Czech Christian,
Dukart Juergen,
Galasko Douglas,
Foroud Tatiana,
Chahine Lana M.,
Coffey Christopher S.,
Simuni Tanya,
Weintraub Daniel,
Seibyl John,
Poston Kathleen L.,
Toga Arthur W.,
Tanner Caroline M.,
Marek Kenneth,
Hutten Samantha J.,
Dziadek Sebastian,
Trenkwalder Claudia,
Pagano Gennaro,
Mollenhauer Brit
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28608
Subject(s) - homovanillic acid , dopamine , putamen , parkinson's disease , medicine , dopaminergic , cerebrospinal fluid , monoamine neurotransmitter , dopamine transporter , caudate nucleus , endocrinology , psychology , chemistry , disease , serotonin , receptor
Background Cerebrospinal fluid (CSF) levels of monoamine metabolites may represent biomarkers of Parkinson's disease (PD). Objective The aim of this study was quantification of multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis. Methods Absolute levels of multiple monoamine metabolites in CSF were quantified by liquid chromatography coupled with tandem mass spectrometry from 161 individuals with early PD and 115 HCs from the Parkinson's Progression Marker Initiative and de novo PD (DeNoPA) studies. Results Baseline levels of homovanillic acid (HVA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) were lower in individuals with PD compared with HCs. HVA levels correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale total scores ( P < 0.01). Both HVA/dopamine and DOPAC/dopamine levels correlated with caudate nucleus and raw DOPAC with putamen dopamine transporter single‐photon emission computed tomography uptake ratios ( P < 0.01). No metabolite changed over 2 years in drug‐naive individuals, but some changed on starting levodopa treatment. Conclusions HVA and DOPAC CSF levels mirrored nigrostriatal pathway damage, confirming the central role of dopaminergic degeneration in early PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society