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Protein Biomarker Shows Promise for Early Detection of Parkinsonian Disorders

NEW YORK — A team led by scientists at Lund University in Sweden has identified a protein biomarker in cerebrospinal fluid (CSF) and blood plasma that could be useful for the early diagnosis of Parkinsonian disorders. 

Parkinsonian disorders — comprising atypical Parkinson's syndromes as well as Lewy body disease, which includes Parkinson's disease and dementia with Lewy bodies — are among the most common neurodegenerative disorders. Even though there is evidence that the decay of neurons associated with these conditions starts before clinical symptoms appear, no early biomarkers exist to date.

For their studypublished in Nature Aging on Tuesday, the researchers used a multiplex immunoassay from Olink Proteomics to estimate the levels of 2,943 proteins in the CSF of 428 individuals from the Swedish BioFinder 2 cohort, including 347 controls and 81 patients with Lewy body disease. They found that patients had elevated levels of DOPA decarboxylase, an enzyme that converts levodopa into dopamine, which is depleted in patients.

They also noted high CSF DOPA decarboxylase levels in preclinical stages of Lewy body disease, suggesting that it could be a potential marker for detecting preclinical cases with no cognitive impairment and predicting their progression to clinical disease. 

The increased production of DOPA decarboxylase could be a way for neurons that usually receive dopaminergic input to compensate for low dopaminergic levels, the authors hypothesized.

Meanwhile, individuals with atypical Parkinsonian disorders, such as multiple system atrophy, also had increased CSF DOPA decarboxylase levels, but the same wasn't true for people with non-Parkinsonian neurodegenerative diseases.

Because plasma biomarkers are easier to measure, they also looked at the levels of 92 proteins in 174 patients and controls from the BioFinder 1 study, and again, found DOPA carboxylase levels to be significantly elevated in Lewy body disease patients and atypical patients compared to controls.

"Collectively, our findings show that [DOPA decarboxylase] is a unique and very promising biomarker for [Lewy body disease] and atypical Parkinsonian disorders," the authors concluded.

Further, to distinguish Lewy body disease from atypical Parkinsonian disorders, they suggested combining DOPA carboxylase testing with the α-synuclein seed amplification assay, since the latter is specific to Lewy body disease.

"Although we replicated our findings in an independent cohort, future studies are needed to analyze [DOPA decarboxylase] in several cohorts and assess the generalizability of our results across multiple samples," they noted. "Furthermore, we did not have longitudinal [DOPA decarboxylase] data, which will be crucial to determine the clinical value of changes in this biomarker over time."