A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic and prognostic biomarker for Parkinson’s disease

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Background Novel supportive diagnostic and prognostic biomarkers for Parkinson’s disease (PD) are needed to enable its early diagnosis and inform clinical trials. Proteomic studies have identified cerebrospinal fluid (CSF) DOPA decarboxylase (DDC) as a promising biomarker candidate, but its role has not been well characterized. The aim of this study was to gain further insight into the potential of DDC as biomarker for PD. Methods We developed and validated a single molecule counting immunoassay for DDC quantification in CSF based on commercially available monoclonal antibodies. DDC levels were quantified in the Parkinson’s Progression Markers Initiative cohort including healthy controls (n=29), dopaminergic drug-naïve patients with PD (n=27) and with scans without evidence for dopaminergic deficit (SWEDD) (n=18). Their relationship with ioflupane-[123I]-single-photon emission computed tomography-based dopamine transporter (DaT-SPECT) imaging was analyzed. The prognostic potential of CSF DDC was evaluated by assessing the relationship between baseline DDC levels and yearly changes of Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores. CSF DDC levels were also quantified three years after the diagnosis, and their relationship with the L-DOPA equivalent daily dose (LEDD) was investigated. Finally, absolute DDC levels determined by our assay were correlated with relative concentrations obtained from Olink technology. Results Our DDC assay detected elevated levels in CSF from dopaminergic drug-naïve PD patients and discriminated them from untreated SWEDD and control with high sensitivity and specificity. There was an inverse correlation between baseline DDC levels and DaT-SPECT striatal binding ratios (SBR) from the putamen and caudate nucleus. Baseline CSF DDC levels demonstrated prognostic potential for MDS-UPDRS total change five to eight years after the diagnosis. DDC levels were further increased at the three-year follow-up visit in PD patients and were positively correlated with the LEDD. Finally, there was a strong correlation between relative CSF DDC levels determined with the Olink assay and absolute DDC levels determined with our assay. Conclusions Our monoclonal antibody-based assay for DDC quantification provided further insight into the potential of DDC in CSF to serve as a diagnostic and prognostic biomarker for PD. The unchanged levels in SWEDD patients and the inverse correlation with DaT-SPECT SBR suggest that DDC levels in CSF are connected to dopaminergic deficit.

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