Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease

Thomas Kremer; Kirsten I Taylor; Juliane Siebourg-Polster; Thomas Gerken; Andreas Staempfli; Christian Czech; Juergen Dukart; Douglas Galasko; Tatiana Foroud; Lana M Chahine; Christopher S Coffey; Tanya Simuni; Daniel Weintraub; John Seibyl; Kathleen L Poston; Arthur W Toga; Caroline M Tanner; Kenneth Marek; Samantha J Hutten; Sebastian Dziadek; Claudia Trenkwalder; Gennaro Pagano; Brit Mollenhauer

doi:10.1002/mds.28608

Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease

Mov Disord. 2021 Aug;36(8):1972-1978. doi: 10.1002/mds.28608. Epub 2021 May 4.

Authors

Thomas Kremer¹, Kirsten I Taylor^{1

2}, Juliane Siebourg-Polster³, Thomas Gerken⁴, Andreas Staempfli⁵, Christian Czech¹, Juergen Dukart^{1

6

7}, Douglas Galasko⁸, Tatiana Foroud⁹, Lana M Chahine¹⁰, Christopher S Coffey¹¹, Tanya Simuni¹², Daniel Weintraub¹³, John Seibyl¹⁴, Kathleen L Poston¹⁵, Arthur W Toga¹⁶, Caroline M Tanner^{17

18}, Kenneth Marek^{14

19}, Samantha J Hutten¹⁹, Sebastian Dziadek¹, Claudia Trenkwalder^{20

21}, Gennaro Pagano¹, Brit Mollenhauer^{21

22}

Affiliations

¹ Roche Pharmaceutical Research and Early Development, NRD Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
² Faculty of Psychology, University of Basel, Basel, Switzerland.
³ Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
⁴ Metanomics Health GmbH, Berlin, Germany.
⁵ Roche Pharmaceutical Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
⁶ Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Julich, Germany.
⁷ Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
⁸ Department of Neurosciences, University of California, San Diego, San Diego, California, USA.
⁹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
¹⁰ Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹¹ Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
¹² Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹³ Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁴ Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.
¹⁵ Department of Neurology & Neurological Sciences, School of Medicine, Stanford University, Stanford, California, USA.
¹⁶ Laboratory of Neuro Imaging, University of Southern California (USC) Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
¹⁷ Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
¹⁸ Parkinson's Disease Research Education and Clinical Center, San Francisco Veterans Affairs Health Care System, San Diego, California, USA.
¹⁹ The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
²⁰ Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany.
²¹ Paracelsus-Elena-Klinik, Kassel, Germany.
²² Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.

Abstract

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.

Keywords: CSF; Parkinson's disease; biomarker; catecholamine; homovanillic acid; monoamine metabolites; neurotransmitter.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3,4-Dihydroxyphenylacetic Acid
Homovanillic Acid
Humans
Levodopa
Neurotransmitter Agents
Parkinson Disease* / diagnostic imaging
Parkinson Disease* / drug therapy

Substances

Neurotransmitter Agents
3,4-Dihydroxyphenylacetic Acid
Levodopa
Homovanillic Acid

Abstract

Publication types

MeSH terms

Substances

Grants and funding