路易体疾病中血浆多巴脱羧酶水平的升高是由多巴胺能治疗驱动的。

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

作者信息

Bolsewig Katharina, Willemse Eline A J, Sánchez-Juan Pascual, Rábano Alberto, Martínez Minerva, Doecke James D, Bellomo Giovanni, Vermunt Lisa, Alcolea Daniel, Halbgebauer Steffen, In 't Veld Sjors, Mattsson-Carlgren Niklas, Veverova Katerina, Fowler Christopher J, Boonkamp Lynn, Koel-Simmelink Marleen, Hussainali Zulaiga, Ruiters Daimy N, Gaetani Lorenzo, Toja Andrea, Fortea Juan, Pijnenburg Yolande, Lemstra Afina W, van der Flier Wiesje M, Hort Jakub, Otto Markus, Hansson Oskar, Parnetti Lucilla, Masters Colin L, Lleó Alberto, Teunissen Charlotte E, Del Campo Milán Marta

机构信息

Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.

Amsterdam Neuroscience, Neurodegeneration program, Amsterdam UMC, Amsterdam, The Netherlands.

出版信息

Nat Commun. 2025 Jan 29;16(1):1139. doi: 10.1038/s41467-025-56293-z.

DOI:10.1038/s41467-025-56293-z

PMID:39881147

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11779843/

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.

摘要

多巴胺脱羧酶（DDC）已被提议作为一种脑脊液（CSF）生物标志物，其在路易体疾病（LBD）中的浓度会升高，在接受多巴胺能治疗的患者中水平最高。在此，我们通过邻近延伸分析测量了血浆DDC，并评估了多巴胺能治疗在三个独立的LBD队列（重点关注路易体痴呆（DLB）和帕金森病（PD））中的作用：一个尸检确诊队列（n = 71）、一个大型多中心、跨痴呆队列（n = 1498）以及一个具有详细治疗信息的纵向队列（n = 66，中位随访时间[四分位间距] = 4[4, 4]年）。在未进行治疗的情况下，不同LBD与其他疾病组或对照组之间的血浆DDC没有变化。在PD中，DDC水平随时间升高，且与更高剂量的多巴胺能治疗显著相关。这强调了在分析血浆DDC时需要考虑治疗效果，并表明与脑脊液DDC相比，血浆DDC作为LBD的诊断生物标志物用途有限，但可能对治疗监测有价值。