Central and systemic C-type Natriuretic Peptide are both reduced in Parkinson's Disease

Introduction: C-type Natriuretic Peptide is a neuropeptide widely expressed in the central nervous system including dopaminergic neurons projecting to basal ganglia. Previous work shows that concentrations of the peptide in cerebrospinal fluid are depressed in drug naïve PD subjects, decline over time and can be restored by doses of monoamine oxidase inhibitors that delay the need for levodopa. Whether plasma levels are similarly depressed in drug naïve subjects, or affected by dopaminergic drugs, is unknown. Our objectives were to determine whether (i) peptide products in plasma differ from normal in PD, and (ii) levels are affected by dopaminergic treatment.

Methods: Plasma C-type Natriuretic Peptide and amino-terminal proCNP were measured in two groups - 27 drug naïve subjects with PD, and 30 subjects stabilized on dopaminergic drugs for at least 3 years. Values were compared with standard deviation scores from a population reference group without neurological disorder. Independent associations with predetermined variables known to affect plasma concentrations were assessed by multivariate analysis.

Results: In both PD groups, plasma amino-terminal proCNP was significantly depressed compared to the reference range. Concentrations did not differ between the two groups. No correlation with disease duration or phenotype was found. Across all subjects, in a model initially comprising 7 factors, serum creatinine, PD and age were independent significant associations with amino-terminal proCNP.

Conclusions: Plasma concentrations of amino-terminal proCNP are depressed in PD, are likely to result from diminished reabsorption from central sources, and may be useful in monitoring onset and effects of therapeutic interventions in PD.