TY - JOUR
T1 - Increased plasma DOPA decarboxylase levels in Lewy body disorders are driven by dopaminergic treatment
AU - Bolsewig, K.
AU - Willemse, E.A.J.
AU - Sánchez-Juan, P.
AU - Rábano, Alberto
AU - Martínez, M.
AU - Doecke, J.D.
AU - Bellomo, Giovanni
AU - Vermunt, L.
AU - Alcolea, Daniel
AU - Halbgebauer, S.
AU - in 't Veld, S.
AU - Mattsson-Carlgren, N.
AU - Veverova, K.
AU - Fowler, C.J.
AU - Boonkamp, L.
AU - Koel-Simmelink, M.
AU - Hussainali, Z.
AU - Ruiters, D.N.
AU - Gaetani, L.
AU - Toja, A.
AU - Fortea, Juan
AU - Pijnenburg, Y.
AU - Lemstra, A.W.
AU - van der Flier, W.M.
AU - Hort, J.
AU - Otto, M.
AU - Hansson, Oskar
AU - Parnetti, Lucilla
AU - Masters, C.L.
AU - Lleó, Alberto
AU - Teunissen, C.E.
AU - Del Campo Milán, Marta
PY - 2025/1/29
Y1 - 2025/1/29
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.
KW - Aged
KW - Aged, 80 and over
KW - Biomarkers
KW - Cohort Studies
KW - Dopa Decarboxylase
KW - Dopamine Agents
KW - Female
KW - Humans
KW - Lewy Body Disease
KW - Longitudinal Studies
KW - Male
KW - Middle Aged
KW - Parkinson Disease
UR - https://www.scopus.com/pages/publications/85217357764
UR - https://www.mendeley.com/catalogue/ed2b306e-7826-38b0-9eed-fd135ae3e0ad/
U2 - 10.1038/s41467-025-56293-z
DO - 10.1038/s41467-025-56293-z
M3 - Article
C2 - 39881147
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1139
ER -