Longitudinal Evaluation of 18 F-MK-6240 Along the Alzheimer Disease Continuum

Understanding the rate of tau accumulation is critical for staging Alzheimer disease (AD), monitoring its progression, and informing clinical trial design. Although PET imaging with 18F-MK-6240, also known as florquinitau, can track tau pathology, longitudinal data remain limited. We evaluated longitudinal tau changes using 18F-MK-6240 PET across cognitive stages and analyzed regional rates of change with the goal of informing future clinical trial outcome measures. Methods: In this observational study, 27 participants with varying cognitive statuses (cognitively unimpaired CU, mild cognitive impairment MCI, and AD) underwent 18F-MK-6240 PET at baseline and at 6, 12, and 24 mo (or at 18 and 30 mo during the COVID-19 pandemic). Amyloid positivity at baseline was determined with 11C-labeled Pittsburgh compound B PET. Tau PET data were analyzed as SUV ratios (SUVRs) in regions of interest (ROIs) corresponding to Braak staging as well as the inferior temporal gyrus and 2 composite ROIs (metatemporal composite MTC) and an early tau composite. Annualized SUVR changes were compared across groups and correlated with cognitive scores (Mini-Mental State Examination, Clinical Dementia Rating Scale, and the Alzheimer’s Disease Assessment Scale–Cognitive Subscale) using the Kruskal–Wallis test. Correlations between the change in SUVR and cognitive outcomes were estimated using Spearman ρ. Results: Baseline 18F-MK-6240 PET showed a minimal signal in CU participants, localized signal to the medial temporal lobe in participants with MCI, and a signal spanning the inferolateral temporal lobe and extending posteriorly along the ventral cortex in participants with AD. Longitudinal analysis showed that the annualized percent change in tau deposition in the MTC was 0.17% ± 4.16, 5.77% ± 2.97, and 4.31% ± 5.84 in the CU, MCI, and AD groups, respectively (P = 0.075). The change in tau deposition was 0.00 ± 0.05, 0.10 ± 0.07, and 0.12 ± 0.16 in the CU, MCI, and AD groups, respectively (P = 0.039). Tau accumulation correlated with a decline on the Alzheimer Disease Assessment Scale–Cognitive Subscale (ρ = 0.43, P Conclusion:18F-MK-6240 PET tracked tau accumulation over time and provided preliminary evidence that these changes correlate with cognitive decline, supporting its utility for longitudinal AD studies and trial design, with MTC emerging as a promising ROI for clinical trials.