TY - JOUR
T1 - Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment
AU - Bolsewig, Katharina
AU - Willemse, Eline A. J.
AU - Sánchez-Juan, Pascual
AU - Rábano, Alberto
AU - Martínez, Minerva
AU - Doecke, James D.
AU - Bellomo, Giovanni
AU - Vermunt, Lisa
AU - Alcolea, Daniel
AU - Halbgebauer, Steffen
AU - in 't Veld, Sjors
AU - Mattsson-Carlgren, Niklas
AU - Veverova, Katerina
AU - Fowler, Christopher J.
AU - Boonkamp, Lynn
AU - Koel-Simmelink, Marleen
AU - Hussainali, Zulaiga
AU - Ruiters, Daimy N.
AU - Gaetani, Lorenzo
AU - Toja, Andrea
AU - Fortea, Juan
AU - Pijnenburg, Yolande
AU - Lemstra, Afina W.
AU - van der Flier, Wiesje M.
AU - Hort, Jakub
AU - Otto, Markus
AU - Hansson, Oskar
AU - Parnetti, Lucilla
AU - Masters, Colin L.
AU - Lleó, Alberto
AU - Teunissen, Charlotte E.
AU - del Campo Milán, Marta
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85217357764
U2 - 10.1038/s41467-025-56293-z
DO - 10.1038/s41467-025-56293-z
M3 - Article
C2 - 39881147
SN - 2041-1723
VL - 16
SP - 1139
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1139
ER -