Longitudinal serum uric acid levels are not associated with dopamine transporter binding in progressive supranuclear palsy.

UNLABELLED: Progressive supranuclear palsy (PSP) causes rapid motor decline and severe dopaminergic dysfunction. While uric acid (UA) may act as a neuroprotective antioxidant in some neurodegenerative disorders (like Parkinson’s disease), its role in PSP remains unclear. This study evaluated the relationship between serum UA levels, measured cross-sectionally and longitudinally, and striatal dopamine transporter binding in PSP. A total of 33 PSP patients with repeated pre-[123I]FP-CIT SPECT UA measurements, along with 30 healthy control individuals and 30 patients with Alzheimer’s disease (AD), were retrospectively analyzed. Group and sex effects were analyzed with t tests and ANOVA. Effects of mean UA and longitudinal UA trajectories on FP-CIT SPECT binding in PSP were modeled using linear mixed-effects models and regressed against binding in four regions (caudate and putamen), separated into more-affected and less-affected side for both sexes. A Bayesian two-stage measurement-error model provided sensitivity analysis. UA was significantly lower in PSP (4.98 mg/dl) and AD (4.69 mg/dl) compared to healthy controls (5.71 mg/dL; p = 0.001). Sex had a significant effect on UA (F(1, 89) = 9.38, p = 0.003, partial η2 = 0.10), however, this effect was significant only in PSP (p< 0.001). Within PSP, UA–[123I]FP-CIT SPECT correlations were weak and nonsignificant, and neither UA intercept nor slope predicted [123I]FP-CIT SPECT binding (all p > 0.7). Bayesian estimates corroborated the absence of a credible relationship. In the present cohort, serum UA is reduced in PSP, primarily in females, but neither mean levels nor longitudinal changes are related to striatal [123I]FP-CIT SPECT binding, suggesting no clear association with dopaminergic degeneration in PSP, without precluding a potential role of uric acid at other disease stages.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00702-026-03141-z.