Study Rationale: We know that genetics plays a role in risk of Parkinson’s disease (PD) but does not explain every case, leading to the suggestion that genes work within the context of other exposures in the environment. We think that there are a subtype of brain cells, called microglia, that may be sensitive to environmental changes as these are immune cells of the brain and may have immunological ‘memory’.
Hypothesis: Human derived cells, namely microglia, will change in response to environmentally relevant exposures in a way that changes their DNA in the long term.
Study Design: We will take induced pluripotent stem cells that were generously donated by participants in the PPMI study and convert them into microglia. We will use a range of toxins that are present in the environment and expose cells to concentrations that do not simply kill cells and see how their DNA responds. We will also look at how the same exposures change interactions between microglia and dopamine neurons.
Impact on Diagnosis/Treatment of Parkinson’s disease: We predict that we will be able to combine genetic predictors with environmental exposures to better explain overall lifetime risk of PD.
Next Steps for Development: If we are right and we see stable changes in cells in an experimental setting, in future work we would like to go back and compare with human Parkinson’s disease to see if we can back calculate what a given person had been exposed to in their lifetime.