Temporal Trajectories Of In Vivo Tau And Amyloid-Beta Accumulation In Alzheimer'S Disease

Purpose To investigate the temporal trajectories of tau and amyloid-beta (A beta) 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 F-18-flortaucipir and F-18-florbetaben PET studies with a mean follow-up time of 2 years. Referencing baseline data from 57 A beta-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 A beta 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 A beta, while the rise in global cortical A beta curve preceded that for global cortical tau. A beta accumulation rate was attenuated during the surge in tau burden in the global cortex and reached a plateau. Conclusion Sequential appearance of A beta and tau accumulation supports a hypothetical dynamic biomarker model and Braak's hierarchical tau spreading model in AD.