Baek Min Seok, Cho Hanna, Lee Hye Sun, Choi Jae Yong, Lee Jae Hoon, Ryu Young Hoon, Lee Myung Sik, Lyoo Chul Hyoung
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
Eur J Nucl Med Mol Imaging. 2020 Nov;47(12):2879-2886. doi: 10.1007/s00259-020-04773-3. Epub 2020 Apr 29.
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 F-flortaucipir and F-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.
通过纵向正电子发射断层扫描（PET）研究，调查阿尔茨海默病（AD）中tau蛋白和淀粉样β蛋白（Aβ）积累的时间轨迹。
共有132名参与者，包括健康志愿者或在我们记忆障碍诊所招募的人员，完成了纵向F-氟代tau蛋白配体和F-氟代贝他班PET研究，平均随访时间为2年。以57名Aβ阴性认知未受损个体的基线数据为参照，在校正部分容积效应后，根据基线和随访时测量的全脑皮质或区域标准化摄取值比率计算Z分数及其年度变化。基于年度变化和基线Z分数数据的样条模型，得出tau蛋白和Aβ负担随时间变化的时间轨迹。
tau蛋白负担首先出现在Braak分期的I-II期区域，随后是III-IV期区域，最后是V-VI期区域。Z分数曲线上升超过2的两个时间点之间的时间间隔，I-II期和III-IV期为17.3年，III-IV期和V-VI期为15.2年。I-II期tau蛋白曲线的上升先于全脑皮质Aβ曲线，而全脑皮质Aβ曲线的上升先于全脑皮质tau蛋白曲线。在全脑皮质tau蛋白负担激增期间，Aβ积累速率减弱并达到平台期。
Aβ和tau蛋白积累的顺序出现支持了AD中假设的动态生物标志物模型和Braak的tau蛋白分层扩散模型。
