Objective: To assess the correlation of CSF DDC levels to DaT-SPECT SBR in PD and iRBD.

Background: Raised cerebrospinal fluid (CSF) proteomic biomarker, DOPA decarboxylase (DDC), is described in Parkinson’s Disease (PD) and idiopathic REM-sleep behaviour disorder (iRBD)/ prodromal synuclein disease. This is likely due to compensatory mechanisms amidst a growing dopamine deficiency, demonstrated by the negative correlation between CSF DDC levels and DaT-SPECT striatal binding ratios (SBR) in levodopa-treated PD.

Method: A total of 19 subjects (7 PD, 11 iRBD and 1 healthy control) with matching DaT-SPECT and CSF DDC levels were included from the Oxford Parkinson’s Disease Centre’s Discovery Cohort. DDC levels were analysed using proximity extension assay and correlated with DaT-SPECT SBR. Further analysis correlated CSF DDC levels to levodopa equivalent daily dose (LEDD) and measures of motor symptom severity, Hoehn and Yahr (HY) staging.

Results: Our analysis suggest CSF DDC levels have an inverse correlation with DaT-SPECT SBR in levodopa-treated PD subjects, which was not seen in prodromal and drug-naïve PD. Furthermore, CSF DDC levels correlated positively in subjects with more severe disease, as measured with HY staging.

Conclusion: The correlation between CSF DDC, DaT SPECT SBR and HY shown in this small group of levodopa-treated PD replicates a prior publication and extended analysis into prodromal disease. We conclude that CSF DDC levels likely track PD motor symptom severity and, rather than being a drug effect, signifies compensatory upregulation in response to reduced dopaminergic neuronal survival. We also highlight that raised CSF DDC levels in iRBD or drug-naïve PD does not mirror striatal dopamine deficiency, as measured by DaT SPECT.

Figure 1

Figure 2

Figure 3

Figure 4

References: 1. Khosousi S, Sturchio A, Appleton E, et al. Increased CSF DOPA Decarboxylase Correlates with Lower DaT-SPECT Binding: Analyses in Biopark and PPMI Cohorts. Movement Disorders. Published online October 1, 2024. doi:10.1002/mds.29835
2. Rutledge J, Lehallier B, Zarifkar P, et al. Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson’s disease. Acta Neuropathol. 2024;147(1). doi:10.1007/s00401-024-02706-0

« Back to 2025 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-dopa-decarboxylase-levels-as-a-marker-of-disease-severity-in-parkinsons-disease/