Serum Uric Acid Levels in Parkinson’s Disease: A Cross-Sectional Electronic Medical Record Database Study from a Tertiary Referral Centre in Romania

Abstract

Background and Objectives: Parkinson’s disease (PD) is a prevalent neurodegenerative condition responsible for progressive motor and non-motor symptoms. Currently, no prophylactic or disease-modifying interventions are available. Uric acid (UA) is a potent endogenous antioxidant, resulting from purine metabolism. It is responsible for about half of the antioxidant capacity of the plasma. Increasing evidence suggests that lower serum UA levels are associated with an increased risk of developing PD and with faster disease progression. Materials and Methods: We conducted an electronic medical record database study to investigate the associations between UA levels and different characteristics of PD. Results: Out of 274 datasets from distinct patients with PD, 49 complied with the predefined inclusion and exclusion criteria. Lower UA levels were significantly associated with the severity of parkinsonism according to the Hoehn and Yahr stage (rs = 0.488, p = 0.002), with the motor complications of long-term dopaminergic treatment (r = 0.333, p = 0.027), and with the presence of neurocognitive impairment (r = 0.346, p = 0.021). Conclusion: Oxidative stress is considered a key player in the etiopathogenesis of PD, therefore the involvement of lower UA levels in the development and progression of PD is plausible. Data on the potential therapeutic roles of elevating serum UA (e.g., by precursor administration or diet manipulation) are scarce, but considering the accumulating epidemiological evidence, the topic warrants further research.

Purine and lipid metabolism in rats with a rotenone model of Parkinson’s disease under the influence of methanindiazenone

“…Postmortem tissue studies have shown low urate levels in the substantia nigra in patients with PD. In animal models, UA has a neuroprotective effect on dopaminergic neurons due to the modulation of neuroinflammation and oxidative stress [31]. Based on our results, it can be assumed that in PD, an increase in hypoxanthine levels indicates a decrease in its conversion to UA efficiency.…”

Moderating effects of uric acid and gender on non-motor symptoms in asymmetric Parkinson's disease

“…The reason behind this divergence in literature could possibly arise from the inclusion of PD patients at variable stages of the disease. In early-stage PD, lower serum UA could be an indicator of an endogenic capacity to cope with PD-related cerebral oxidative stress induced by multiple neuropathological factors, such as protein misfolding, mitochondrial dysfunction, excitotoxicity, etc., 29,30 . Thus, decreased UA serum concentrations in early PD patients could re ect an e cient mobilization of peripheral antioxidant resources to the brain.…”

“…This phenomenon has also been observed in post-traumatic brain injury studies showing that decreased UA serum levels concurred with increased UA concentrations in damaged brain tissues 28 . With time however, the body's natural defenses seem to become insu cient, moreso given decreased UA production as the disease progresses, coupled by its excessive consumption in PD 23,29 . Thus, at more advanced stages of PD, patients maintaining higher concentrations of serum UA might be more advantaged compared to patients exhibiting de cit levels of UA.…”

“…One plausible explanation behind lowered concentrations of serum UA in PD can reside in the phenomenon of peripheral mobilization of antioxidant resources 28 . Indeed, UA seems to be excessively consumed in PD, presumably as a result of important cerebral oxidative stress taking place during the course of the disease 29,30 . Levodopa medication might further amplify this process through cerebral dopamine oxidation (Dănău et al, 2022).…”

“…Indeed, UA seems to be excessively consumed in PD, presumably as a result of important cerebral oxidative stress taking place during the course of the disease 29,30 . Levodopa medication might further amplify this process through cerebral dopamine oxidation (Dănău et al, 2022). As such, peripheral UA would be actively recruited to compromised brain tissues in order to participate in an endogenous oxidative defense.…”