Summary: An international research consortium has identified a quantitative biomarker in cerebrospinal fluid (CSF) that markedly improves diagnostic accuracy for Parkinson’s disease and Lewy body dementia (LBD). The protein DOPA decarboxylase (DDC), essential to dopamine synthesis, was found at substantially higher concentrations in affected patients and can reliably distinguish these disorders from Alzheimer’s disease.
Researchers measured DDC in lumbar (spinal) fluid and found concentrations up to 2.5 times higher in people with Parkinson’s disease or LBD than in healthy controls. Importantly, DDC levels were also measurably higher in these disorders than in Alzheimer’s disease, giving clinicians an objective biochemical marker to reduce misdiagnosis and enable earlier, more appropriate treatment decisions.
Key Facts
- Specificity versus Alzheimer’s: CSF DDC concentrations are significantly elevated in Parkinson’s disease and LBD compared with Alzheimer’s disease, supporting clear differential diagnosis where symptoms often overlap.
- Dopamine pathway link: DDC is the enzyme that converts L-DOPA to dopamine. Its presence in CSF reflects pathological changes in dopamine-producing brain regions.
- High sensitivity assays: The consortium developed two highly sensitive immunoassays that consistently measured DDC increases—up to about 250% higher in the affected groups versus healthy controls.
- Clinical correlation: Higher CSF DDC levels correlated with the presence of pathological brain changes and, in some cohorts, with progression of α-synuclein pathology, supporting the biomarker’s biological relevance.
The study was led by Dr. Katharina Bolsewig and Professor Charlotte Teunissen of the Laboratory of Neurochemistry at the Amsterdam UMC, with key contributions from Dr. Sebastiaan Engelborghs, Professor at Vrije Universiteit Brussel (VUB) and Head of Neurology at UZ Brussel. Their team focused on measuring DDC in CSF to determine whether it could serve as a reliable disease marker.
Across multiple clinical cohorts, the researchers validated two independent DDC immunoassays and conducted extensive clinical testing. CSF DDC was consistently higher in patients with Parkinson’s disease and dementia with Lewy bodies than in healthy control subjects, and also higher than in patients diagnosed with Alzheimer’s disease. The assays produced strong diagnostic performance, with area under the curve values exceeding 0.9 for differential diagnosis in the tested cohorts.
Professor Engelborghs emphasised the clinical implications: dementia with Lewy bodies is often misdiagnosed because its symptoms overlap with other dementias. Misdiagnosis can lead to inappropriate or even harmful treatments. An objective CSF biomarker such as DDC can guide clinicians to the correct diagnosis sooner, improving patient management and treatment decisions.
In addition to the diagnostic distinctions, the study found a relationship between elevated CSF DDC and biologically defined measures of disease. For example, in an autopsy-confirmed cohort, higher CSF DDC correlated with increasing α-synuclein pathology. Immunohistochemical analysis showed colocalisation of DDC and α-synuclein in the substantia nigra, supporting a mechanistic link between the biomarker and the underlying disease process.
Although these findings strongly support the clinical value of CSF DDC, the authors note that further standardisation and broader implementation studies are required before routine clinical use. The consortium highlights the importance of international collaboration in moving this biomarker from research into practice.
Key Questions Answered:
A: Symptoms overlap substantially between these conditions, so clinical assessment alone often leads to misdiagnosis. A biochemical marker like CSF DDC offers an objective “chemical signature” to separate them with greater accuracy.
A: DOPA decarboxylase is the enzyme that converts L-DOPA into dopamine. When dopaminergic neurons are damaged in disorders such as Parkinson’s disease or LBD, this enzyme is released and its concentration rises in the cerebrospinal fluid.
A: Indirectly. Earlier and more accurate diagnosis helps ensure patients receive the most appropriate treatments and avoid therapies that could be ineffective or harmful, improving long-term care and management.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed for this report.
- Additional context was provided by editorial staff.
About this neurology research news
Author: Koen Stein
Source: VUB
Contact: Koen Stein – VUB
Image: Image credited to Neuroscience News
Original Research: Open access. “A quantitative DOPA decarboxylase biomarker for diagnosis in Lewy body disorders” by Katharina Bolsewig et al., published in 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 and misdiagnosis can result in inappropriate or harmful treatment choices. DOPA decarboxylase (DDC) is a promising cerebrospinal fluid biomarker for DLB and Parkinson’s disease (PD), but clinical adoption requires robust quantitative assays.
This study describes two newly developed DDC immunoassays and their validation across several clinical cohorts (total n = 740), a biologically defined cohort (n = 253), a cohort with dopamine transporter imaging (n = 102) and an autopsy-confirmed cohort (n = 78). CSF DDC was significantly elevated in DLB and PD—up to 2.5-fold versus controls and about 1.9-fold versus Alzheimer’s disease—with diagnostic performance showing area under the curve values greater than 0.9 for differential diagnosis.
Elevated CSF DDC associated with the presence of motor impairment and, in autopsy-confirmed cases, correlated with advancing α-synuclein pathology. Immunohistochemistry showed colocalisation of DDC and α-synuclein in the substantia nigra, strengthening the biological rationale for DDC as a disease marker.
These results support the clinical value of CSF DDC to aid diagnosis of DLB and PD and provide a path forward for implementation using the immunoassays developed in this work.