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

Bolsewig, Katharina ; Willemse, Eline A.J. ; Sánchez-Juan, Pascual ; Rábano, Alberto ; Martínez, Minerva ; Doecke, James D. ; Bellomo, Giovanni ; Vermunt, Lisa ; Alcolea, Daniel and Halbgebauer, Steffen , et al. (2025) In Nature Communications 16(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
16
issue
1
article number
1139
publisher
Nature Publishing Group
external identifiers
  • pmid:39881147
  • scopus:85217357764
ISSN
2041-1723
DOI
10.1038/s41467-025-56293-z
language
English
LU publication?
yes
id
b16e39c4-d829-4f4c-9a93-1034a91b1777
date added to LUP
2025-04-01 15:45:25
date last changed
2025-07-08 23:42:58
@article{b16e39c4-d829-4f4c-9a93-1034a91b1777,
  abstract     = {{<p>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.</p>}},
  author       = {{Bolsewig, Katharina and Willemse, Eline A.J. and Sánchez-Juan, Pascual and Rábano, Alberto and Martínez, Minerva and Doecke, James D. and Bellomo, Giovanni and Vermunt, Lisa and Alcolea, Daniel and Halbgebauer, Steffen and in ‘t Veld, Sjors and Mattsson-Carlgren, Niklas and Veverova, Katerina and Fowler, Christopher J. and Boonkamp, Lynn and Koel-Simmelink, Marleen and Hussainali, Zulaiga and Ruiters, Daimy N. and Gaetani, Lorenzo and Toja, Andrea and Fortea, Juan and Pijnenburg, Yolande and Lemstra, Afina W. and van der Flier, Wiesje M. and Hort, Jakub and Otto, Markus and Hansson, Oskar and Parnetti, Lucilla and Masters, Colin L. and Lleó, Alberto and Teunissen, Charlotte E. and Del Campo Milán, Marta}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-56293-z}},
  doi          = {{10.1038/s41467-025-56293-z}},
  volume       = {{16}},
  year         = {{2025}},
}