natriuretic-peptide--c-type and Cognition-Disorders

C-type natriuretic peptide (CNP) is a neurotrophic factor widely expressed in the central nervous system including the basal ganglia, limbic system and hypothalamus. Nothing is known of CNP's role in the human brain but in rodents CNP promotes axon growth and branching, and interacts with dopaminergic function in models of addiction. Because preliminary evidence showed reduced levels in Parkinson's disease (PD), we examined concentrations of CNP peptides in cerebrospinal fluid (CSF) in 146 PD patients from the DATATOP study to determine changes over time in relation to medication status and cognitive function. CNP and an aminoterminal product of proCNP (NTproCNP) were measured in extracts from stored CSF by radioimmunoassay. CSF samples were obtained twice-at enrolment and at the study's endpoint (requirement for levodopa treatment) after treatment with placebo or deprenyl. At enrolment, median baseline concentration of CSF NTproCNP (776 pmol/L, n = 146) was significantly lower than that in a reference group without neurological disorder (1,010 pmol/L, p < 0.001). Concentrations declined significantly during placebo (p = 0.02) and lower values at enrolment were associated with more rapid functional decline (p < 0.01). In contrast, deprenyl-a treatment which delayed the need for levodopa-nullified the time-dependent decline in CSF NTproCNP. In conclusion subnormal CSF NTproCNP which declines with time and associates with increasing functional disability implicates CNP in PD. Concordant clinical and peptide responses to deprenyl suggest that some of the benefits of monoamine oxidase inhibitors in PD are mediated by preserving tissue CNP activity.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cognition Disorders; Female; Humans; Male; Middle Aged; Natriuretic Peptide, C-Type; Parkinson Disease; Retrospective Studies; Selegiline; Severity of Illness Index; Time Factors