Longitudinal plasma phosphorylated tau217 classification and the association with Alzheimer's disease progression
Abstract
Abstract INTRODUCTION Longitudinal diagnostic and prognostic validity of plasma phosphorylated tau217 (p‐tau217) in Alzheimer's disease (AD) remains uncertain. METHODS In this multi‐cohort study of 2117 individuals, we established baseline plasma p‐tau217 thresholds for amyloid‐β–positron emission tomography (Aβ‐PET) and assessed their longitudinal classification stability and prognostic relevance for AD‐related outcomes. RESULTS Baseline‐defined cutoffs achieved high and sustained accuracy (86%–95%) for Aβ‐PET positivity over up to 5 years of follow‐up. Longitudinally, most p‐tau217–positive individuals remained stable (93%–98%), whereas the intermediate zone group progressed more to positive (44%–78%) than p‐tau217–negative individuals (4%–21%). Participants with stable‐positive and progress‐to‐positive p‐tau217 profiles more frequently exhibited Aβ abnormalities (90%–100% and 64%–96%, respectively) and experienced accelerated tau accumulation, hippocampal atrophy, and incident dementia compared to those with a stable‐negative p‐tau217 profile. DISCUSSION These findings support the high stability and Aβ‐PET classification performance of longitudinal plasma p‐tau217 monitoring in AD, providing a scalable tool for risk stratification and disease monitoring.
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Authors: Guoyu Lan, Wang Liao, Mingxing Jiang, Jiayi Zhu, Wenqing Ran, Fernando Gonzalez‐Ortiz, Xiang Fan, 杨洪杰, Dai Shi, Laihong Zhang, Anqi Li, Yue Cai, Pan Sun, Zhengbo He, Xin Zhou, Jie Yang, Yalin Zhu, Mingxu Li, Wenjing Huang, Binhui Liu, Yiying Wang, Xinyue Ma, Rong Ma, Yimei Zhang, Chao Huang, Zhen Liu, Qingyong Wang, Liemin Zhou, Fang Xie, Ying Han, Zhen Liang, Xuhui Chen, Mengjie Dong, Guanxun Cheng, Lu Wang, Benyan Luo, Yan‐Jiang Wang, Xiaochun Chen, for the Alzheimer's Disease Neuroimaging Initiative, Jiawei Xin, Guoping Peng, Tengfei Guo
Institutions: First Affiliated Hospital Zhejiang University, Fudan University, Sun Yat-sen University, South China University of Technology, Harbin Institute of Technology, Fujian Medical University, Army Medical University, Union Hospital, Guangzhou Medical University, Second Affiliated Hospital of Guangzhou Medical University, Westlake University, Capital Medical University, University of Gothenburg, Hong Kong University of Science and Technology, Shenzhen Bay Laboratory, Hainan University, Peking University Shenzhen Hospital, First Affiliated Hospital of Jinan University, Daping Hospital, Shenzhen Academy of Aerospace Technology, Huashan Hospital, The Seventh Affiliated Hospital of Sun Yat-sen University, ShenZhen People’s Hospital