Objective/Rationale:
Oxidative damage to brain cells — akin to rust on car parts — can build up in Parkinson’s disease (PD) and leads to break down of brain functions. Urate is a natural antioxidant that can protect brain cells in the laboratory. Uniquely, urate in blood or brain fluid has also been found to be a molecular predictor (‘biomarker’) of both a reduced risk and a slower decline of typical PD. We aim to find out whether urate and structurally related molecules (collectively known as purines) might be biomarkers of protection against a form of PD caused by LRRK2 gene mutations. We hypothesize that urate levels will be higher in people who do not have PD despite having the LRRK2 mutation.
Project Description:
Blood samples from people with PD and the LRRK2 mutation, people without PD but carrying the mutation, and people without PD or the mutation will be analyzed using validated laboratory measurements of a range of purines including urate, and of total antioxidant capacity.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If the project provides evidence that purines are biomarkers in the subset of PD triggered by LRRK2 gene mutations, then those purines may be pursued for their potential impact on predicting PD risk in LRRK2 carriers. Similarly, the mechanism by which any implicated purine(s) might interact with LRRK2 may then be explored; purine-elevating treatments may be a candidate strategy to prevent PD in LRRK2+ carriers.
Anticipated Outcome:
Whereas the present study is based on a ‘snapshot’ of PD status, future studies could directly test predictive power of such purines by following PD status over years to determine, for example, whether LRRK2+ carriers with higher urate take longer to develop PD.