CSF DOPA Decarboxylase emerging biomarker for Parkinsonian disorders

In a significant stride towards early detection and prognosis of Parkinsonian disorders, a recent study published in the Nature Aging Journal revealed the potential of cerebrospinal fluid levels of DOPA decarboxylase (DDC) as a highly accurate biomarker.

Currently, the diagnosis of Parkinsonian disorders heavily relies on clinical criteria, which tend to have limited sensitivity until a substantial loss of dopaminergic neurons has occurred. However, this new research has unveiled the remarkable ability of DDC to pinpoint Lewy body disease (LBD) with an impressive accuracy rate. The area under the curve (AUC) stands at 0.89, with a false discovery rate (FDR) of 2.6 x 10^-13, making it a highly reliable diagnostic tool.

Moreover, the study suggests that DDC levels are not only linked to the presence of LBD but also correlate with cognitive decline. Patients with elevated DDC levels exhibited worse cognitive performance, reinforcing the significance of this biomarker in understanding and managing these conditions.

One of the most exciting findings is that DDC can detect preclinical stages of LBD, even in individuals who are clinically asymptomatic but test positive for abnormal alpha-synuclein through a seed amplification assay. With an AUC of 0.81 and a P-value of 1.0 x 10^-5, this discovery could lead to early intervention and treatment strategies for those at risk. 

Additionally, the research suggests that DDC levels can predict the progression from preclinical stages to clinical LBD over a three-year period. The hazard ratio for this transition is 3.7 per standard deviation change, further underlining DDC's potential as a prognostic tool.

Remarkably, elevated DDC levels were also observed in atypical Parkinsonian disorders, setting it apart from non-Parkinsonian neurodegenerative disorders. These findings were replicated in an independent cohort, where it was further demonstrated that DDC levels in plasma can serve as an effective diagnostic marker for both LBD and atypical Parkinsonian disorders.

With further validation and refinement, DDC could soon become an essential tool in clinical practice, allowing for timely intervention and improved outcomes for patients with these challenging conditions.

Source:

Pereira, J. B., Kumar, A., Hall, S., Palmqvist, S., Stomrud, E., Bali, D., Parchi, P., Mattsson-Carlgren, N., Janelidze, S., & Hansson, O. (2023). DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease. In Nature Aging. Springer Science and Business Media LLC. https://doi.org/10.1038/s43587-023-00478-y