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Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease.
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.
Afiliação
  • Kremer T; Roche Pharmaceutical Research and Early Development, NRD Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Taylor KI; Roche Pharmaceutical Research and Early Development, NRD Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Siebourg-Polster J; Faculty of Psychology, University of Basel, Basel, Switzerland.
  • Gerken T; Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Staempfli A; Metanomics Health GmbH, Berlin, Germany.
  • Czech C; Roche Pharmaceutical Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Dukart J; Roche Pharmaceutical Research and Early Development, NRD Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Galasko D; Roche Pharmaceutical Research and Early Development, NRD Neuroscience and Rare Diseases, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
  • Foroud T; Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre Jülich, Julich, Germany.
  • Chahine LM; Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • Coffey CS; Department of Neurosciences, University of California, San Diego, San Diego, California, USA.
  • Simuni T; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Weintraub D; Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Seibyl J; Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
  • Poston KL; Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
  • Toga AW; Department of Neurology Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Tanner CM; Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.
  • Marek K; Department of Neurology & Neurological Sciences, School of Medicine, Stanford University, Stanford, California, USA.
  • Hutten SJ; 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.
  • Dziadek S; Department of Neurology, University of California, San Francisco, San Francisco, California, USA.
  • Trenkwalder C; Parkinson's Disease Research Education and Clinical Center, San Francisco Veterans Affairs Health Care System, San Diego, California, USA.
  • Pagano G; Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.
  • Mollenhauer B; The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
Mov Disord ; 36(8): 1972-1978, 2021 08.
Article em En | MEDLINE | ID: mdl-33942926
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson Idioma: En Ano de publicação: 2021 Tipo de documento: Article