바로가기  >

이달의 연구자 바로가기 Click!

Abstract
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.

정상인 평균에서 2 standard deviation 이상 증가하는 것을 cut-off로 생각했을 때 amyloid-β는 16.2년 뒤에 유의미하게 늘어나기 시작해서 약 40여년 뒤에는 plateau에 도달하며, tau는 32.5년 뒤부터 유의미한 수준 이상으로 증가하기 시작해서 지속적으로 증가하는 패턴의 trajectory를 보이고 있다.

Affiliations

Min Seok Baek  1 , Hanna Cho  1 , Hye Sun Lee  2 , Jae Yong Choi  3   4 , Jae Hoon Lee  3 , Young Hoon Ryu  5 , Myung Sik Lee  1 , Chul Hyoung Lyoo  6
1 Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
2 Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
3 Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
4 Division of RI-Convergence Research, Korea Institute Radiological and Medical Sciences, Seoul, South Korea.
5 Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. ryuyh@yuhs.ac.
6 Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea. lyoochel@yuhs.ac.