Summary: An international consortium discovered a breakthrough quantitative biomarker in cerebrospinal fluid (CSF) that significantly improves the diagnostic accuracy for Parkinson’s disease and Lewy body dementia (LBD). The study identifies the protein DOPA decarboxylase—essential for dopamine production—as a highly specific indicator of these diseases.
Concentrations of the protein in lumbar fluid were found to be up to 2.5 times higher in affected patients compared to healthy controls. Crucially, this biomarker can differentiate LBD from Alzheimer’s disease, providing clinicians with an objective tool to prevent misdiagnosis and ensure appropriate treatment from an early stage.
Key Facts
- Specificity Over Alzheimer’s: Unlike many general neurological markers, DOPA decarboxylase levels are significantly higher in Parkinson’s and LBD than in Alzheimer’s, allowing for clear differentiation between these overlapping conditions.
- Dopamine Link: DOPA decarboxylase is a key enzyme in the synthesis of dopamine; its elevated presence in CSF directly reflects the pathological changes occurring in the brain’s dopamine-producing regions.
- High Sensitivity: The consortium developed two specialized laboratory tests that showed protein levels in the target group were up to 250% higher than in healthy individuals.
- Clinical Accuracy: Higher concentrations of the biomarker were found to correlate directly with the severity of pathological brain changes, underlining its reliability as a diagnostic tool.
Source: VUB
An international consortium has achieved a major breakthrough in the diagnosis of neurological diseases.
In a recent publication in the scientific journal Nature Medicine, they describe the discovery of a new quantitative biomarker in lumbar fluid (cerebrospinal fluid) that is helping doctors to diagnose Parkinson’s disease and Lewy body dementia more accurately.
The consortium, led by Dr Katharina Bolsewig and Prof Charlotte Teunissen of the Laboratory of Neurochemistry at the UMC in Amsterdam, with the essential contribution of Dr Sebastiaan Engelborghs, Professor at the VUB and Head of the Department of Neurology at UZ Brussel, focused on the protein DOPA decarboxylase. This protein plays a crucial role in the production of dopamine in the brain.
The study shows that the concentration of DOPA decarboxylase in cerebrospinal fluid is significantly higher in patients with Parkinson’s disease or Lewy body dementia. This difference is even clearly measurable compared with patients suffering from Alzheimer’s disease, making the test highly specific.
Professor Engelborghs: “The importance of this discovery for clinical practice is considerable, as dementia with Lewy bodies is often difficult to diagnose correctly at present. Because of the strong overlap of symptoms with other forms of dementia, patients are regularly misdiagnosed. Misdiagnosis can lead to less effective or, in some cases, harmful treatment. The new measurement method provides doctors with an objective tool for determining the right course of action at an early stage”.
In the course of the study, the consortium developed two highly sensitive laboratory tests to reliably record the presence of DOPA decarboxylase. The results show that values in the target group are up to two and a half times higher than in healthy control subjects. In addition, a higher concentration of the biomarker correlated directly with the degree of pathological changes in the brain, underlining the biological relevance of the test.
Although these results represent a significant step towards everyday application in healthcare, the consortium stresses that further standardisation is required. “We can speak of a fruitful international collaboration. This publication brings a crucial biomarker closer to the patient, precisely in cases where diagnosis is still too often associated with uncertainty,” concludes Engelborghs.
Key Questions Answered:
A: Their symptoms overlap heavily, leading to frequent misdiagnoses. Until now, doctors relied largely on clinical observation. This new test provides an objective “chemical signature” to tell them apart with high accuracy.
A: It’s an enzyme your brain uses to make dopamine. When the brain’s dopamine systems are damaged by diseases like Parkinson’s, this protein “leaks” into the cerebrospinal fluid in much higher concentrations.
A: Indirectly, yes. By ensuring the correct diagnosis earlier, patients can avoid treatments that might be ineffective or even harmful for their specific condition, leading to much better long-term management.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neurology research news
Author: Koen Stein
Source: VUB
Contact: Koen Stein – VUB
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders” by Katharina Bolsewig, Giovanni Bellomo, Yanaika S. Hok-A-Hin, Imane Al Idrissi, Lisa Vermunt, Alberto Lleó, Daniel Alcolea, Anne Sieben, Sebastiaan Engelborghs, Anja Hviid Simonsen, Steen G. Hasselbalch, Sara Bech, Tjado H. J. Morrema, Jeroen J. M. Hoozemans, John G. J. M. Bol, Juliette van Alphen, Lorenzo Gaetani, Davide Chiasserini, Federico Paolini Paoletti, Lucilla Parnetti, Sungwoo Kang, Young-gun Lee, Suhee Jeon, Ahreum Lee, Seun Jeon, Byoung Seok Ye, Marta del Campo Milán, Wiesje M. van der Flier, Wilma D. J. van de Berg, Afina W. Lemstra, Eline A. J. Willemse & Charlotte E. Teunissen. Nature Medicine
DOI:10.1038/s41591-026-04212-0
Abstract
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.
