A monoclonal antibody-based immunoassay reinforces DOPA decarboxylase in cerebrospinal fluid as a diagnostic biomarker for Parkinson's disease with potential prognostic value

BackgroundProteomic studies have identified cerebrospinal fluid (CSF) DOPA decarboxylase (DDC) as a promising biomarker candidate for Parkinson's disease (PD). The aim of this study was to develop an immunoassay for CSF DDC quantification and gain further insight into its potential as a biomarker for PD.MethodsWe validated our DDC immunoassay by quantifying CSF DDC levels in the Parkinson's Progression Markers Initiative cohort, including healthy controls (n = 29), dopaminergic drug-naïve PD patients (n = 27), and patients with scans without evidence for dopaminergic deficit (SWEDD) (n = 18).ResultsOur DDC assay detected elevated levels in CSF from dopaminergic drug-naïve PD patients and discriminated them against SWEDD patients and controls with high sensitivity and specificity. There was an inverse correlation between DDC levels and ioflupane-[123I]-single-photon emission computed tomography-based dopamine transporter (DaT-SPECT) striatal binding ratios (SBRs) from the putamen and caudate nucleus. CSF DDC levels demonstrated prognostic potential for Movement Disorder Society Unified Parkinson's Disease Rating Scale total score change five to eight years post-diagnosis. DDC levels were further increased at the three-year follow-up visit in PD patients and positively correlated with the L-DOPA equivalent daily dose. There was a strong correlation between the relative CSF DDC levels determined by a proprietary immune-based proximity extension assay and absolute levels determined with our assay.ConclusionsOur assay provided further insight into the potential of CSF DDC as a diagnostic and prognostic biomarker for PD. The unchanged levels in SWEDD patients and inverse correlation with DaT-SPECT SBRs suggest that CSF DDC levels are connected to dopaminergic deficit.