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



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.


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.


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.


Sequential appearance of Aβ and tau accumulation supports a hypothetical dynamic biomarker model and Braak’s hierarchical tau spreading model in AD.

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We express our special appreciation to Tae Ho Song and Won Taek Lee (PET technologists) who managed all PET scans with enthusiasm.


This research was supported by a grant from Korean Neurological Association (KNA-19-MI-12), faculty research grant of Yonsei University College of Medicine for (6-2018-0068), Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2017R1A2B2006694) and the Ministry of Education (NRF-2018R1D1A1B07049386), and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1159).

Author information




Y. H. Ryu Conception and design, Administrative support, Collection and assembly of data, Data analysis and interpretation, Supervision, Final approval of manuscript

C. H. Lyoo Conception and design, Administrative support, Collection and assembly of data, Data analysis and interpretation, Manuscript writing, Final approval of manuscript

Corresponding authors

Correspondence to Young Hoon Ryu or Chul Hyoung Lyoo.

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This study was approved by the institutional review board of Gangnam Severance Hospital and written informed consent was obtained from all participants.

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Baek, M., Cho, H., Lee, H. et al. Temporal trajectories of in vivo tau and amyloid-β accumulation in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 47, 2879–2886 (2020). https://doi.org/10.1007/s00259-020-04773-3

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  • Alzheimer’s disease
  • Positron emission tomography
  • Tau
  • 18F-flortaucipir