Bakshi R, et al. - In this investigation, researchers ascertained if urate, an antioxidant, Nrf2 activator and an inverse risk factor for idiopathic Parkinson's disease (PD), is one such candidate biomarker of PD risk modulation in pathogenic mutation carriers of LRRK2. In order to carry out a pilot study of 192 subjects from the LRRK2 Cohort Consortium (LCC) and two validation studies of 380 other subjects from the LCC and 922 subjects from the Parkinson Progression Marker Initiative, banked plasma samples or urate levels were obtained for three cohorts of age- and sex-matched subjects with and without a known LRRK2 mutation in the PD and unaffected controls. Investigators found that non-manifested carriers of LRRK2 mutations had significantly higher urate levels than those who developed PD in each of the three independent cohorts. A meta-analysis showed an adjusted mean difference of 0.62 mg/dL, with similar results for separate evaluations of men and women. An increase in urate concentration of 2 mg/dL reduced the probability of PD by more than 50%. These findings identify and substantiate urate among LRRK2 mutation carriers as a biomarker of PD resistance.