DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment. DDC levels increased over time in PD, being significantly associated to higher dosages of dopaminergic treatment. This emphasizes the need to consider treatment effect when analyzing plasma DDC, and suggests that plasma DDC, in contrast to CSF DDC, is of limited use as a diagnostic biomarker for LBD, but could be valuable for treatment monitoring.

Alzheimer's Centre Reina Sofia CIEN Foundation ISCIII Madrid Spain

Amsterdam Neuroscience Neurodegeneration program Amsterdam UMC Amsterdam The Netherlands

Australian E Health Research Centre CSIRO Herston QLD Australia

Barcelonaβeta Brain Research Center Pasqual Maragall Foundation Barcelona Spain

Centro de Investigación Biomédica en Red en enfermedades neurodegenerativas Instituto de Salud Carlos 3 Madrid Spain

Clinical Memory Research Unit Lund University Lund Sweden

Departamento de Ciencias Farmacéuticas y de la Salud Facultad de Farmacia Universidad San Pablo CEU CEU Universities Madrid Spain

Department of Clinical Research University Hospital Basel University of Basel Basel Switzerland

Department of Epidemiology and Biostatistics Amsterdam Neuroscience Amsterdam UMC Amsterdam The Netherlands

Department of Neurology Alzheimer Center Amsterdam Amsterdam UMC Amsterdam The Netherlands

Department of Neurology Institut d'Investigacions Biomèdiques Sant Pau Hospital de Sant Pau Universitat Autònoma de Barcelona Hospital de la Santa Creu 1 Sant Pau Barcelona Spain

Department of Neurology University Hospital and University of Basel Basel Switzerland

Department of Neurology University Hospital Ulm Ulm Germany

Florey Institute The University of Melbourne Melbourne VIC Australia

German Center for Neurodegenerative Diseases Ulm Germany

Hospital del Mar Research Institute Barcelona Spain

Memory Clinic Department of Neurology Charles University 2nd Faculty of Medicine and Motol University Hospital Prague Czech Republic

Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel Department of Biomedicine and Clinical Research University Hospital and University of Basel Basel Switzerland

Neurochemistry Laboratory Department of Laboratory Medicine Amsterdam Neuroscience VU University Medical Center Amsterdam UMC Amsterdam The Netherlands

Neurology Clinic Skåne University Hospital Lund Sweden

Section of Neurology Laboratory of Clinical Neurochemistry Department of Medicine and Surgery University of Perugia Perugia Italy

Wallenberg Center for Molecular Medicine Lund University Lund Sweden

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