Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment
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.
Authors
- Lisa Vermunt (ORCID: https://orcid.org/0000-0001-7420-6384)
- Minerva Martínez (ORCID: https://orcid.org/0000-0002-9036-2595)
- Sjors in ‘t Veld
- Juan Fortea (ORCID: https://orcid.org/0000-0002-1340-638X)
- Alberto Lleó (ORCID: https://orcid.org/0000-0002-2568-5478)
- Steffen Halbgebauer (ORCID: https://orcid.org/0000-0002-8711-5702)
- James D. Doecke (ORCID: https://orcid.org/0000-0003-2863-0293)
- Lucilla Parnetti (ORCID: https://orcid.org/0000-0001-5722-3967)
- Eline A.J. Willemse (ORCID: https://orcid.org/0000-0001-9140-4243)
- Andrea Toja (ORCID: https://orcid.org/0009-0000-9500-7632)
- Afina W. Lemstra (ORCID: https://orcid.org/0000-0002-8933-3260)
- Wiesje M. van der Flier (ORCID: https://orcid.org/0000-0001-8766-6224)
- Daimy N. Ruiters
- Zulaiga Hussainali
- Marta del Campo (ORCID: https://orcid.org/0000-0003-2808-3699)
- Niklas Mattsson (ORCID: https://orcid.org/0000-0002-8885-7724)
- Oskar Hansson (ORCID: https://orcid.org/0000-0001-8467-7286)
- Katharina Bolsewig (ORCID: https://orcid.org/0000-0003-3116-7789)
- Christopher J. Fowler (ORCID: https://orcid.org/0000-0002-6658-7874)
- Pascual Sánchez‐Juan
- Giovanni Bellomo (ORCID: https://orcid.org/0000-0003-0456-5650)
- Markus Otto (ORCID: https://orcid.org/0000-0003-4273-4267)
- Charlotte Elisabeth Teunissen (ORCID: https://orcid.org/0000-0002-4061-0837)
- Kateřina Veverová (ORCID: https://orcid.org/0000-0002-5845-1854)
- Alberto Rábano (ORCID: https://orcid.org/0000-0001-9320-6566)
- Jakub Hort (ORCID: https://orcid.org/0000-0002-1080-3726)
- Daniel Alcolea (ORCID: https://orcid.org/0000-0002-3819-3245)
- Lorenzo Gaetani (ORCID: https://orcid.org/0000-0003-3967-8954)
- Yolande A.L. Pijnenburg (ORCID: https://orcid.org/0000-0003-2464-1905)
- Colin L. Masters
- Lynn Boonkamp
- Marleen J.A. Koel‐Simmelink (ORCID: https://orcid.org/0000-0003-3939-7394)
Institutions
- Universidad San Pablo CEU (ES)
- Universitat Autònoma de Barcelona (ES)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- The University of Melbourne (AU)
- University of Basel (CH)
- Lund University (SE)
- Charles University (CZ)
- Florey Institute of Neuroscience and Mental Health (AU)
- University of Perugia (IT)
- Instituto de Salud Carlos III (ES)
- German Center for Neurodegenerative Diseases (DE)
- Hospital de Sant Pau (ES)
- University Hospital of Basel (CH)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Pasqual Maragall Foundation (ES)
- Amsterdam Neuroscience (NL)
- Centro de Investigación Biomédica en Red (ES)
- Barcelonaβeta Brain Research Center (ES)
- Skåne University Hospital (SE)
- Australian e-Health Research Centre (AU)
- Amsterdam University Medical Centers (NL)
- Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES)
- University Hospital Ulm (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-29
- DOI
- https://doi.org/10.1038/s41467-025-56293-z
- Citations
- 12
- Primary Topic
- Genetic Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 10.91
Funders
- European Commission
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- National Institutes of Health
- Horizon 2020 Framework Programme
- Instituto de Salud Carlos III
- European Regional Development Fund
- National Institute on Aging