Cerebrospinal fluid dopa-decarboxylase is a biomarker of dopaminergic dysfunction
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Background
Nigrostriatal dopaminergic dysfunction, a biological anchor of Parkinson’s disease (PD), is routinely assessed using single-photon emission computed tomography of the dopamine transporter (DaT-SPECT). Dopa decarboxylase (DDC) in cerebrospinal fluid (CSF) is a promising biomarker of dopaminergic dysfunction, but its association with DaT-SPECT has to be demonstrated.
Objectives
To investigate the association of CSF DDC with DaT-SPECT.
Methods
We first analysed proteomic and DaT-SPECT data from the Parkinson’s Progression Markers Initiative (PPMI), including PD (n=891), prodromal PD (n=867) and healthy controls (n=161). We then verified this association in a single-center clinical cohort (UNIPG), including PD/Dementia with Lewy Bodies (DLB) (n=78), atypical parkinsonisms (AP, n=11), other neurodegenerative diseases (OND, n=25) and controls (CTRL, n=40). Here, CSF DDC was measured by a novel fully automated quantitative immunoassay.
Results
In PPMI, among 129 proteins assessed, DDC showed the strongest association with DaT-SPECT (β = −0.132, FDR = 6.92 × 10 −33 ). Across PPMI and UNIPG cohorts, DDC correlated with striatal binding ratio (SBR) (ρ = −0.377, P < 0.001; ρ = −0.466, P < 0.001, respectively) and accurately discriminated positive from negative scans (AUC 0.811, 95% CI 0.762–0.859; AUC 0.870, 95% CI 0.777–0.963, respectively). In PPMI prodromal cases, higher DDC predicted faster motor progression. In UNIPG, DDC distinguished PD/DLB and AP from OND and CTRL groups (AUC 0.830, 95% CI 0.764–0.896), independently of dopaminergic treatment.
Conclusion
CSF DDC reflects nigrostriatal dopaminergic dysfunction, representing a potential quantitative biochemical alternative to DaT-SPECT that might be readily implemented via automated immunoassays.
