Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

Abstract

Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology.

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“…Although uric acid plays a vital role in biological processes at low concentrations, [ 1 ] long‐term accumulation leads to the formation of monosodium urate crystals and subsequently leads to gout, renal injury, and metabolic disorders. [ 2 ] Uric acid is mainly produced in the liver and is metabolized via cooperative excretion by multiple transporters in the kidney. [ 3 ] Therefore, compounds that inhibit uric acid synthesis and promote excretion have been widely used to reduce uric acid levels in patients with hyperuricemia.…”

Bioactive Compounds from Plant-Based Functional Foods: A Promising Choice for the Prevention and Management of Hyperuricemia

“…Hyperuricemia (HUA) is a common metabolic disease caused by an imbalance between endogenous production and excretion of urate [1]. Recently, considerable evidence has indicated that uric acid (UA), an endogenous antioxidant present in low concentrations in the human plasma, plays an active role in life processes [2,3]. However, the over-production of UA easily results in the formation of monosodium urate crystals, which increases inflammation and causes gout [4].…”

What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease

“…One measure of oxidative stress is uric acid (UA), the most abundant naturally occurring, strong antioxidant both in the CNS and in the periphery [ 76 ]. Evidence for the neuroprotective effect of uric acid has been provided by the results of studies, including clinical studies, for PD, indicating its potential as a biomarker of reduced risk of morbidity and milder progression of PD [ 77 , 78 ].…”