Postmortem Brain Levels of Urate and Precursors in Parkinson's Disease and Related Disorders

Abstract

Background: Increasing evidence suggests that urate may play an important role in neurodegenerative disease. In Parkinson's disease (PD) higher, but still normal, levels of blood and cerebrospinal fluid urate have been associated with a lower rate of disease progression. Objective: We explored the hypothesis that lower levels of urate and its purine precursors in brain may be associated with PD and related neurodegenerative disorders, including Alzheimer's disease (AD) and Lewy body dementia (DLB). Methods: Human postmortem brain tissues were obtained from PD, AD, and DLB patients and non-neurodegenerative disease controls. We measured urate and other purine pathway analytes in the frontal and temporal cortex, striatum, and cerebellum, using high-performance liquid chromatography with electrochemical and ultraviolet detection. Results: Age was well-matched among groups. Mean postmortem interval for samples was 16.3 ± 9.9 h. Urate levels in cortical and striatal tissue trended lower in PD and AD compared to controls in males only. These findings correlated with increased urate in male versus female control tissues. By contrast, in DLB urate levels were significantly elevated relative to PD and AD. Measurement of urate precursors suggested a decrease in xanthine in PD compared to AD in females only, and relative increases in inosine and adenosine in DLB and AD samples among males. Xanthine and hypoxanthine were more concentrated in striatal tissue than in other brain regions. Conclusions: Though limited in sample size, these findings lend support to the inverse association between urate levels and PD, as well as possibly AD. The finding of increased urate in DLB brain tissue is novel and warrants further study.