Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment
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 in ‘t Veld, Niklas Mattsson, Kateřina Veverová, Christopher J. Fowler, Lynn Boonkamp, Marleen J.A. Koel‐Simmelink, Zulaiga Hussainali, Daimy N. Ruiters, Lorenzo Gaetani, Andrea Toja, Juan Fortea, Yolande A.L. Pijnenburg, Afina W. Lemstra, Wiesje M. van der Flier, Jakub Hort, Markus Otto, Oskar Hansson, Lucilla Parnetti, Colin L. Masters, Alberto Lleó, Charlotte E. Teunissen, Marta del Campo
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. DOPA decarboxylase (DDC) in cerebrospinal fluid has great diagnostic potential for Lewy body disorders. Here, the authors report limited diagnostic potential of plasma DDC and a strong association with dopaminergic treatment.