- Kremer, Thomas;
- Taylor, Kirsten I;
- Siebourg‐Polster, 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
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.