Temporal trajectories of in vivo tau and amyloid-β accumulation in Alzheimer’s disease

Purpose: To investigate the temporal trajectories of tau and amyloid-β (Aβ) accumulation in Alzheimer’s disease (AD) by using the longitudinal positron emission tomography (PET) study. Methods: A total of 132 participants, who were healthy volunteers or recruited in our memory disorder clinic, completed longitudinal ¹⁸F-flortaucipir and ¹⁸F-florbetaben PET studies with a mean follow-up time of 2 years. Referencing baseline data from 57 Aβ-negative cognitively unimpaired individuals, Z-scores and their annual changes were calculated with the global cortical or regional standardized uptake value ratios measured at baseline and follow-up after correcting for partial volume effect. The temporal trajectories of tau and Aβ burden as a function of time were obtained based on the spline models from the annual changes and baseline Z-score data. Results: Tau burden first emerged in the Braak’s stage I–II regions, followed by stage III–IV regions, and finally in the stage V–VI regions. Time intervals between two time points at which Z-score curves rose above 2 were 17.3 years for the stages I–II and III–IV and 15.2 years for the stages III–IV and V–VI. Rise in the tau curve for stages I–II preceded that for global cortical Aβ, while the rise in global cortical Aβ curve preceded that for global cortical tau. Aβ accumulation rate was attenuated during the surge in tau burden in the global cortex and reached a plateau. Conclusion: Sequential appearance of Aβ and tau accumulation supports a hypothetical dynamic biomarker model and Braak’s hierarchical tau spreading model in AD.