Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment

Katharina Bolsewig (k.bolsewig@amsterdamumc.nl), Eline A. J. Willemse, Pascual Sánchez-Juan, Alberto Rábano, Minerva Martínez, James D. Doecke, Giovanni Bellomo, Lisa Vermunt, Daniel Alcolea, Steffen Halbgebauer, Sjors in ‘t Veld, Niklas Mattsson-Carlgren, Katerina Veverova, Christopher J. Fowler, Lynn Boonkamp, Marleen Koel-Simmelink, Zulaiga Hussainali, Daimy N. Ruiters, Lorenzo Gaetani, Andrea Toja, Juan Fortea, Yolande Pijnenburg, Afina W. Lemstra, Wiesje M. Flier, Jakub Hort, Markus Otto, Oskar Hansson, Lucilla Parnetti, Colin L. Masters, Alberto Lleó, Charlotte E. Teunissen and Marta Campo Milán
Additional contact information
Katharina Bolsewig: VU University Medical Center, Amsterdam UMC
Eline A. J. Willemse: VU University Medical Center, Amsterdam UMC
Pascual Sánchez-Juan: Instituto de Salud Carlos III
Alberto Rábano: Alzheimer’s Centre Reina Sofia-CIEN Foundation-ISCIII
Minerva Martínez: Alzheimer’s Centre Reina Sofia-CIEN Foundation-ISCIII
James D. Doecke: CSIRO
Giovanni Bellomo: University of Perugia
Lisa Vermunt: VU University Medical Center, Amsterdam UMC
Daniel Alcolea: Instituto de Salud Carlos III
Steffen Halbgebauer: University Hospital Ulm
Sjors in ‘t Veld: VU University Medical Center, Amsterdam UMC
Niklas Mattsson-Carlgren: Lund University
Katerina Veverova: Second Faculty of Medicine and Motol University Hospital
Christopher J. Fowler: The University of Melbourne
Lynn Boonkamp: VU University Medical Center, Amsterdam UMC
Marleen Koel-Simmelink: VU University Medical Center, Amsterdam UMC
Zulaiga Hussainali: VU University Medical Center, Amsterdam UMC
Daimy N. Ruiters: VU University Medical Center, Amsterdam UMC
Lorenzo Gaetani: University of Perugia
Andrea Toja: University of Perugia
Juan Fortea: Instituto de Salud Carlos III
Yolande Pijnenburg: Amsterdam UMC
Afina W. Lemstra: Amsterdam UMC
Wiesje M. Flier: Amsterdam UMC
Jakub Hort: Second Faculty of Medicine and Motol University Hospital
Markus Otto: University Hospital Ulm
Oskar Hansson: Lund University
Lucilla Parnetti: University of Perugia
Colin L. Masters: The University of Melbourne
Alberto Lleó: Instituto de Salud Carlos III
Charlotte E. Teunissen: VU University Medical Center, Amsterdam UMC
Marta Campo Milán: VU University Medical Center, Amsterdam UMC

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-56293-z

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