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DETECTION OF TAU ACCUMULATION IN AMYLOID POSITIVE PRECLINICAL AND EARLY AD USING [18F]RO-948, [18F]MK-6240, [18F]GTP1, AND [18F]FLORTAUCIPIR TAU PET TRACERS
Abstract
Aims
This study aims to evaluate the ability of [18F]RO-948, [18F]MK-6240, [18F]GTP1, and [18F]flortaucipir tau PET tracers to detect longitudinal changes in amyloid positive cognitive unimpaired (Aβ+CU) and mild cognitive impaired (Aβ+MCI) subjects.
Methods
A total of 341 participants underwent tau PET at baseline and after one year using either [18F]RO-948 (n=13 Aβ+CU, 23 Aβ+MCI), [18F]MK-6240 (n=30 Aβ+CU, 37 Aβ+MCI), [18F]GTP1 (n=5 Aβ+CU, 126 Aβ+MCI), or [18F]flortaucipir (n=61 Aβ+CU, 46 Aβ+MCI). Amyloid positivity was assessed using quantitative amyloid PET when available or via either PET visual read or CSF Aβ42/40. Annualized SUVR changes in Braak I/II and Braak III/IV were calculated using a Freesurfer based pipeline, with whole cerebellar cortex as reference region. Cohen’s D longitudinal effect size was computed for each cohort. 95% confidence intervals (CIs) were calculated using a bootstrap approach.
Results
In Aβ+CU (Figure 1), [18F]RO-948 and [18F]MK-6240 had comparable effect sizes in Braak I/II region (0.61±0.27 and 0.72±0.18, respectively), whereas [18F]flortaucipir did not detect any longitudinal change. The [18F]GTP1 Aβ+CU results were not reliable because only 5 subjects, younger and with significantly lower amyloid load were imaged. In Aβ+MCI (Figure 2), all tracers had comparable effect sizes in Braak III/IV region (range: 0.50-0.62).
Conclusions
Though cohort differences precluded cross-cohort evaluations, both [18F]RO-948 and [18F]MK-6240 could detect longitudinal changes in Braak I/II in Aβ+CU after one year, while no changes were detectable with [18F]flortaucipir and not enough data was available for [18F]GTP1. All tracers performed similarly in Aβ+MCI. Head-to-head studies are needed to confirm these results.