Elevated cerebrospinal fluid (CSF) levels of the enzyme DOPA decarboxylase (DDC) may help support the diagnosis of Lewy body disorders such as Parkinson’s disease and dementia with Lewy bodies, according to a multicohort analysis published in Nature Medicine.

 

Researchers measured CSF DDC concentrations across six independent cohorts that included patients with Parkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease, and cognitively healthy controls. Across cohorts, CSF DDC concentrations were higher in Lewy body disorders than in controls and Alzheimer’s disease, supporting the biomarker’s potential role in differential diagnosis.

 

Models incorporating CSF DDC, age, and sex demonstrated strong diagnostic performance, with high accuracy for distinguishing Lewy body disorders from controls and moderate-to-high accuracy compared with Alzheimer’s disease.

 

By contrast, plasma DDC showed no diagnostic value. Blood concentrations did not differ significantly across diagnostic groups in the biologically defined cohort and were elevated primarily among patients receiving dopaminergic therapy.

 

Higher CSF DDC levels were also associated with certain clinical features of dementia with Lewy bodies. Patients with parkinsonian symptoms or visual hallucinations had higher DDC concentrations than those without these features, whereas no associations were observed for other core features such as cognitive fluctuations or REM sleep behavior disorder. CSF DDC levels were not associated with motor impairment severity.

 

Additional analyses linked CSF DDC concentrations with measures of Lewy body pathology. Higher levels were associated with greater alpha-synuclein burden and more advanced Lewy body staging in neuropathologic samples, suggesting the biomarker reflects disease-related changes in affected brain regions.

 

DDC plays a key role in dopamine synthesis, and the researchers proposed that elevated CSF concentrations may reflect dopaminergic neuronal dysfunction or degeneration, although the precise mechanism remains uncertain.

 

The findings suggest that CSF DDC may serve as a supportive biomarker to aid in the diagnosis and biological characterization of Lewy body disorders in clinical and research settings. However, further studies are needed to evaluate performance in broader and longitudinal patient populations and across disease stages.

 

The study authors reported a range of relationships with industry, while others declared no competing interests.

 

Source: Nature Medicine