Abstract

Levodopa induced dyskinesias (LID) are a common problem which ultimately limit the effective treatment of patients with Parkinson's disease (PD). There is accumulating evidence that LID develop due to abnormal synaptic plasticity which is in turn influenced by the release of Brain Derived Neurotrophic factor (BDNF). In this study we have looked at the influence of a common functional polymorphism of the BDNF gene on the risk of developing dyskinesias in a large cohort of patients with PD (n=315), who were independently and variably treated with levodopa and/or other dopaminergic treatments. We found that patients with the met allele of BDNF, associated with lower activity dependent secretion of BDNF, are at significantly higher risk of developing dyskinesias earlier in the course of treatment with dopaminergic agents (HR for each additional met allele 2.12, p=0.001), which persists following adjustment for potential confounding variables. This suggests that this functional polymorphism may help predict which individuals are most at risk of LID and is consistent with the known actions of BDNF on synaptic plasticity in the striatum.