Utility of 18F-Florzolotau PET as a prognostic and monitoring biomarker in a memory clinic cohort

Tau PET is increasingly recognized for its prognostic and disease-monitoring value in Alzheimer’s disease (AD); however, real-world evidence in heterogeneous memory clinic populations remains limited, especially for novel tau positron emission tomography (PET) with 18F-Florzolotau. We prospectively enrolled 340 individuals (patients with cognitive complaints and community volunteers) undergoing baseline amyloid PET and tau PET with 18F-Florzolotau, with subsets for clinical follow-up (n = 260; median interval 1.45 [0.96–2.56] years) and repeat tau PET (n = 64; median interval 2.27 [1.47–2.88] years). The incremental prognostic role of tau PET beyond demographic and clinical characteristics was assessed using binary clinical outcomes and continuous cognitive declines. The monitoring utility of tau PET was evaluated through tau accumulation rates versus clinical outcomes, and cognition-tau correlations. Cross-sectionally, tau standardized uptake value ratios (SUVRs) increased with cognitive impairment severity and correlated with domain-specific deficits. Longitudinally, baseline tau SUVRs provided incremental prognostic value, with higher neocortical SUVR as the sole independent predictor beyond demographic and clinical characteristics, particularly in AD spectrum (HR = 1.62, p = 0.018). Accelerated tau deposition was observed in motor regions including the precentral gyrus (β = 0.07 SUVR/year, p = 0.007) and supplementary motor area (β = 0.08 SUVR/year, p = 0.017) in those clinically progressive individuals than stable counterparts. Critically, these motor regions showed stronger cognition-tau correlations than canonical tau-vulnerable regions (medial temporal lobe and neocortex), establishing them as superior monitoring biomarkers. 18F-Florzolotau PET provides significant prognostic value and enables AD progression tracking. Motor cortices offered enhanced sensitivity for monitoring clinical deterioration in symptomatic stages, supporting their integration into stage-specific frameworks.