Alzheimer's Imaging Consortium

The Joint Propagation Model (JPM)-based CenTauR scale was recently introduced to harmonize tau-PET quantification across different radiotracers. This study examined how CenTauR harmonization enhances the comparability of tau-PET quantification across matched cohorts using different tracers. The evaluation focused on three key aspects: (1) comparing tau-PET positivity rates as defined by CenTauR, (2) evaluating its diagnostic accuracy for symptomatic AD, and (3) analyzing longitudinal changes in tau-PET rates over time.

The JPM, developed by the CPAD-led Tau PET Harmonization Working Group (Leuzy et al., Alzheimers Dement. 2024; Figure 1A), models relationships between anchor point subjects and head-to-head tau-PET SUVR data onto the CenTauR scale, providing conversion equations for multiple tracers. JPM equations were applied to [¹⁸F]flortaucipir SUVR (Meta-temporal ROI) data from 561 cognitively impaired participants in the ADNI and OASIS-3 studies. Using ROC analysis, we determined the CenTauR cut-off for positivity (T+) that maximized the Youden index for discriminating between FDA-approved positive/negative visual reads. Three separate cohorts, scanned using [¹⁸F]flortaucipir (ADNI), [¹⁸F]MK-6240 (CPAS), and [¹⁸F]RO-948 (BioFINDER-2), were matched 1:1 by age, MMSE, amyloid-β, and clinical diagnosis. CenTauR-based metrics were compared across these cohorts.

A cut-off of 18 CenTauRs was found to optimally classify [¹⁸F]flortaucipir PET visual reads (Figure 1B). The matching procedure identified 1089 participants (363 per cohort). The frequency of T+ using the 18 CenTauRs cut-off for the Meta-Temporal ROI was highly comparable across tracers across groups, except for the Aβ-positive cognitively unimpaired group, where variability was more pronounced due to a smaller sample size (Figure 2A). Similarly, tau-PET discriminative accuracy for symptomatic AD vs controls remained similar across [¹⁸F]flortaucipir and [¹⁸F]MK-6240 (Figure 2B). In a separate sample of 212 matched participants from ADNI ([¹⁸F]flortaucipir) and AIBL ([¹⁸F]MK-6240) with baseline and 1-year follow-up tau-PET scans, 1-year change in CenTauRs was comparable (Figure 2C). An exploratory voxelwise transformation, utilizing the Meta-Temporal conversion equation in a representative case scanned with both [¹⁸F]flortaucipir and [¹⁸F]MK-6240, demonstrates the potential for voxelwise CenTauR harmonization (Figure 3).

These analyses suggest that CenTauR harmonization increases the comparability of tau-PET data acquired with different tracers. Additional validation analyses with larger cohorts including other radiotracers ([¹⁸F]PI-2620) are underway.