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A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders
Katharina Bolsewig, Giovanni Bellomo, Yanaika Sylvana Hok-A-Hin, Imane Al Idrissi, Lisa Vermunt, Alberto Lleó, Daniel Andres Alcolea, Anne Sieben et al.. Nature Medicine, 2026-02-16
Topic: Brain proteins, microglia and lab models
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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Bolsewig, K., Bellomo, G., Hok-A-Hin, Y. S., Idrissi, I. A., Vermunt, L., Lleó, A., et al. (2026). A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders. Nature Medicine. https://doi.org/10.1038/s41591-026-04212-0
Vancouver
Bolsewig K, Bellomo G, Hok-A-Hin YS, Idrissi IA, Vermunt L, Lleó A, et al. A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders. Nature Medicine. 2026. doi:10.1038/s41591-026-04212-0. PMID: 41699128.
BibTeX
@article{bolsewig2026-41699128,
author = {Bolsewig, Katharina and Bellomo, Giovanni and Hok-A-Hin, Yanaika Sylvana and Idrissi, Imane Al and Vermunt, Lisa and Lleó, Alberto and Alcolea, Daniel Andres and Sieben, Anne and others},
title = {{A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders}},
journal = {Nature Medicine},
year = {2026},
doi = {10.1038/s41591-026-04212-0},
pmid = {41699128},
url = {https://doi.org/10.1038/s41591-026-04212-0}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- 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.
- 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.
Why it matters
This study developed and validated two immunoassays showing that cerebrospinal fluid DOPA decarboxylase levels are higher in dementia with Lewy bodies and Parkinson's disease than in controls or Alzheimer's disease. This is a diagnostic biomarker for Lewy body disorders and does not address treating, curing or preventing Alzheimer's disease.
Study details
- Participants740
- Evidence strengthModerate
How this study scored 59/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature Medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 740 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 5 / 6 | Cited 30.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Charlotte Elisabeth Teunissen: h-index 116 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Copenhagen: institution h-index 1,378 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 33 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41699128) |
| Free to read | 2 / 2 | Free to read |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41591-026-04212-0
- PubMed: 41699128
- Original source →
- Free full text: Nature Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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