CSF Biomarker Improves Diagnosis of Parkinson’s Disease and Lewy Body Dementia

Objective diagnostics for these synucleinopathies remain limited in routine practice, creating uncertainty for clinicians and patients. Earlier, accurate differentiation is needed to guide management and avoid potentially harmful treatments. Researchers now report a quantitative cerebrospinal fluid biomarker that markedly improves diagnostic accuracy.

A research consortium, including Vrije Universiteit Brussel (VUB) and the Laboratory of Neurochemistry at UMC Amsterdam, has identified DOPA decarboxylase (DDC) in cerebrospinal fluid (CSF) as a quantitative biomarker for Parkinson’s disease and dementia with Lewy bodies (DLB), in a study published in Nature Medicine. DDC, an enzyme essential for dopamine synthesis, was measured using two newly developed high-sensitivity immunoassays. The results showed significantly higher CSF DDC concentrations in Parkinson’s disease and DLB compared with Alzheimer’s disease, supporting its potential for differential diagnosis.

The assays quantify DDC in lumbar CSF and reflect pathological changes in dopamine-producing regions. Across validation cohorts, CSF DDC was up to 2.5-fold higher than in healthy controls and 1.9-fold higher than in Alzheimer’s disease. Elevated CSF DDC was linked to the presence, but not the severity, of motor impairment in Parkinson’s disease.

Extensive clinical validation included three clinical cohorts (n=740), one biologically defined cohort (n=253), one cohort with dopamine transporter imaging data (n=102), and one autopsy-confirmed cohort (n=78). Diagnostic performance showed area under the curve values greater than 0.9 for differential diagnosis. In autopsy-confirmed DLB, higher CSF DDC correlated with progressing alpha‑synuclein pathology, and immunohistochemistry in DLB and Parkinson’s disease brain tissue showed colocalization of DDC and alpha‑synuclein in the substantia nigra.

The work, led from Amsterdam UMC with essential contributions from VUB and UZ Brussel, underscores the biomarker’s biological relevance and clinical promise. The consortium noted that further standardization is still required before broader implementation.

“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,” said Sebastiaan Engelborghs, Professor at the VUB and Head of the Department of Neurology at UZ Brussel.

“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,” added Professor Engelborghs.

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Amsterdam UMC
Vrije Universiteit Brussel