A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders

Accurate diagnosis of dementia with Lewy bodies (DLB) remains challenging, with misdiagnosis potentially leading to harmful treatment decisions. DOPA decarboxylase (DDC) shows promise as a cerebrospinal fluid (CSF) biomarker for DLB and Parkinson's disease (PD), but quantitative assays are needed for its clinical implementation. Here we report on the development of two DDC immunoassays and the extensive clinical validation of DDC across three clinical cohorts (n = 740), one biologically defined cohort (n = 253), one cohort with detailed dopamine transporter imaging information (n = 102) and one autopsy-confirmed cohort (n = 78). CSF DDC levels were significantly higher in DLB and PD (up to 2.5-fold versus controls; 1.9-fold versus AD), showing area under the curve values > 0.9 for differential diagnosis. Elevated CSF DDC was linked to the presence, but not severity, of motor impairment. In autopsy-confirmed DLB, higher CSF DDC correlated with progressing α-synuclein pathology and immunohistochemistry in DLB and PD brain tissue revealed colocalization of DDC and α-synuclein in the substantia nigra. These findings underscore DDC's value to support DLB and PD diagnosis, paving the way for its clinical implementation using the here-presented developed immunoassays.

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Publication Details

Journal
Nature Medicine
Published
2026-02-16
DOI
https://doi.org/10.1038/s41591-026-04212-0
Citations
1
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
39.15
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A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders

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Nature Medicine
Parkinson's Disease Mechanisms and Treatments
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article

A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders

Yanaika S. Hok‐A‐Hin, S. Engelborghs, Sára Bech, Davide Chiasserini, Young H. Sohn, Katharina Bolsewig, Giovanni Bellomo, Lorenzo Gaetani, John G. J. M. Bol, Federico Paolini Paoletti, Lisa Vermunt, Eline A J Willemse, Seun Jeon, Sungwoo Kang, Alberto Lleó, Anne Sieben, Wilma D. J. van de Berg, Suhee Jeon, Wiesje M. van der Flier, Steen G. Hasselbalch, Juliette van Alphen, Lucilla Parnetti, Imane Al Idrissi, Jeroen J. M. Hoozemans, Anja Hviid Simonsen, Ahreum Lee, Charlotte E. Teunissen, Afina W. Lemstra, Young-gun Lee, Tjado H. J. Morrema
article en
1 citations

Abstract

Accurate diagnosis of dementia with Lewy bodies (DLB) remains challenging, with misdiagnosis potentially leading to harmful treatment decisions. DOPA decarboxylase (DDC) shows promise as a cerebrospinal fluid (CSF) biomarker for DLB and Parkinson's disease (PD), but quantitative assays are needed for its clinical implementation. Here we report on the development of two DDC immunoassays and the extensive clinical validation of DDC across three clinical cohorts (n = 740), one biologically defined cohort (n = 253), one cohort with detailed dopamine transporter imaging information (n = 102) and one autopsy-confirmed cohort (n = 78). CSF DDC levels were significantly higher in DLB and PD (up to 2.5-fold versus controls; 1.9-fold versus AD), showing area under the curve values > 0.9 for differential diagnosis. Elevated CSF DDC was linked to the presence, but not severity, of motor impairment. In autopsy-confirmed DLB, higher CSF DDC correlated with progressing α-synuclein pathology and immunohistochemistry in DLB and PD brain tissue revealed colocalization of DDC and α-synuclein in the substantia nigra. These findings underscore DDC's value to support DLB and PD diagnosis, paving the way for its clinical implementation using the here-presented developed immunoassays.

Nature MedicineVol. 32(3)
University of Copenhagen (DK), Vrije Universiteit Brussel (BE), University of Antwerp (BE), Yonsei University (KR), University of Perugia (IT), Frederiksberg Hospital (DK), Hospital de Sant Pau (ES), University Hospital of Basel (CH), Copenhagen University Hospital (DK), Rigshospitalet (DK), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Antwerp University Hospital (BE), Pasqual Maragall Foundation (ES), Inje University Ilsan Paik Hospital (KR), Amsterdam Neuroscience (NL), Universitair Ziekenhuis Brussel (BE), Department of Biomedicine Basel (CH), Alzheimer Nederland (NL), Hanyang University Seoul Hospital (KR), GGD Amsterdam (NL), Amsterdam University Medical Centers (NL), Institute of Neurobiology (BG), Link Campus University (IT), Vrije Universiteit Amsterdam (NL)
Good health and well-being
Openalex Percentile: Top 0%
Parkinson's Disease Mechanisms and Treatments
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