Characterizing flortaucipir tau‐PET deposition patterns across the Alzheimer’s disease spectrum: A comparison between regional and whole‐brain approaches

Abstract Background The pattern of tau‐PET deposition might not always follow the classical post‐mortem Braak stages (Vogel et al, 2020). Yet, most current studies use a temporal meta‐ROI to calculate tau‐PET abnormality. We assessed inter‐individual patterns of tau binding across the spectrum of late‐onset Alzheimer’s disease (AD). We computed a score representing the spatial extent uptake of tau‐PET and compared it to a classical temporal meta‐ROI. Method We selected 766 ADNI participants along the AD spectrum (controls [CN], early mild cognitive impairment [eMCI], late MCI [lMCI] and AD patients) who underwent flortaucipir tau‐PET and had an available beta‐amyloid (Aβ)status (Table 1). We fitted 2‐distribution Gaussian mixture‐models to calculate thresholds of liberal and conservative tau retention (50% and 90% probability to be in the high SUVR distribution, respectively) in the classical Braak stages and all 70 FreeSurfer brain regions. Using this categorization, we defined positivity in the different Braak stages (Figure 1A‐C) and individual regions (Figure 1B‐D). We calculated a fine‐grained measure of spatial extent by summing the number of regions showing tau abnormality (Figure 1D and 2A). We also computed a temporal meta‐ROI SUVR (Figure 2B, Jack et al, 2018 regions). Result In Aβ‐positive participants 14% CN, 44% eMCI and 78% lMCI‐AD had elevated SUVRs in Braak stage 1 using the conservative threshold (Figure 1C, yellow). Participants who progressed to subsequent Braak stage(s), defined with conservative thresholds, were positive on all previous stages using a liberal or conservative threshold (Figure 1C yellow and green, 99% of the sample). Only the spatial extent of tau deposition was associated with worse cognition in CN individuals (Figure 3). In AD patients, both greater spatial extent of tau deposition and higher temporal meta‐ROI SUVR were associated with lower cognition, with the spatial extent index showing stronger associations (Figure 3). In AD, further widespread spatial extent and temporal binding was associated with younger age (Figure 4). Conclusion In a typical amnestic cohort of late‐onset AD,the pattern of tau deposition follows the traditional Braak stages. Using a spatial extent index provides stronger results than a temporal‐meta ROI index in detecting associations with cognition.

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