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

Author

Listed:
  • Katharina Bolsewig

    (VU University Medical Center, Amsterdam UMC
    Amsterdam UMC)

  • Eline A. J. Willemse

    (VU University Medical Center, Amsterdam UMC
    University Hospital and University of Basel
    University of Basel
    University Hospital and University of Basel)

  • Pascual Sánchez-Juan

    (Instituto de Salud Carlos III
    Alzheimer’s Centre Reina Sofia-CIEN Foundation-ISCIII)

  • 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
    Amsterdam UMC
    Amsterdam UMC)

  • Daniel Alcolea

    (Instituto de Salud Carlos III
    Hospital de la Santa Creu I Sant Pau)

  • Steffen Halbgebauer

    (University Hospital Ulm
    German Center for Neurodegenerative Diseases (DZNE))

  • Sjors in ‘t Veld

    (VU University Medical Center, Amsterdam UMC
    Amsterdam UMC)

  • Niklas Mattsson-Carlgren

    (Lund University
    Skåne University Hospital
    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
    Amsterdam UMC)

  • Marleen Koel-Simmelink

    (VU University Medical Center, Amsterdam UMC
    Amsterdam UMC)

  • Zulaiga Hussainali

    (VU University Medical Center, Amsterdam UMC
    Amsterdam UMC)

  • Daimy N. Ruiters

    (VU University Medical Center, Amsterdam UMC
    Amsterdam UMC)

  • Lorenzo Gaetani

    (University of Perugia)

  • Andrea Toja

    (University of Perugia)

  • Juan Fortea

    (Instituto de Salud Carlos III
    Hospital de la Santa Creu I Sant Pau)

  • Yolande Pijnenburg

    (Amsterdam UMC
    Amsterdam UMC)

  • Afina W. Lemstra

    (Amsterdam UMC
    Amsterdam UMC)

  • Wiesje M. Flier

    (Amsterdam UMC
    Amsterdam UMC
    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
    Hospital de la Santa Creu I Sant Pau)

  • Charlotte E. Teunissen

    (VU University Medical Center, Amsterdam UMC
    Amsterdam UMC)

  • Marta Campo Milán

    (VU University Medical Center, Amsterdam UMC
    CEU Universities
    Pasqual Maragall Foundation
    Hospital del Mar Research Institute (IMIM))

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.

Suggested Citation

  • Katharina Bolsewig & Eline A. J. Willemse & Pascual Sánchez-Juan & Alberto Rábano & Minerva Martínez & James D. Doecke & Giovanni Bellomo & Lisa Vermunt & Daniel Alcolea & Steffen Halbgebauer & Sjors , 2025. "Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56293-z
    DOI: 10.1038/s41467-025-56293-z
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