Comprehensive evaluation of plasma tau biomarkers for detecting and monitoring Alzheimer's disease in a multicenter and multiethnic aging population

Guoyu Lan; Mengjie Wang; Fernando Gonzalez-Ortiz; Laihong Zhang; Anqi Li; Binyin Li; Mingxing Jiang; Jie Yang; Xuhui Chen; Dai Shi; Xiang Fan; Yue Cai; Pan Sun; Lin Liu; Jieyin Li; Zhengbo He; Lili Fang; Xin Zhou; Linting Chen; Yiying Wang; Mingxu Li; Zhen Liu; Qingyong Wang; Linsen Xu; Liemin Zhou; Guanxun Cheng; Xinlu Wang; Pengcheng Ran; Lu Wang; Kun Sun; Ying Han; Yihui Guan; Kaj Blennow; Fang Xie; Tengfei Guo

doi:10.1038/s43587-025-00904-3

Comprehensive evaluation of plasma tau biomarkers for detecting and monitoring Alzheimer's disease in a multicenter and multiethnic aging population

Nat Aging. 2025 Jun 23. doi: 10.1038/s43587-025-00904-3. Online ahead of print.

Authors

Guoyu Lan^#¹, Mengjie Wang^#², Fernando Gonzalez-Ortiz^#^{3

4}, Laihong Zhang^#^{1

5}, Anqi Li^{1

6}, Binyin Li⁷, Mingxing Jiang^{1

8}, Jie Yang^{1

9}, Xuhui Chen¹⁰, Dai Shi¹¹, Xiang Fan¹², Yue Cai¹, Pan Sun¹, Lin Liu¹, Jieyin Li¹, Zhengbo He^{1

13}, Lili Fang¹, Xin Zhou^{1

14}, Linting Chen^{1

15}, Yiying Wang¹, Mingxu Li¹, Zhen Liu¹, Qingyong Wang¹⁶, Linsen Xu¹⁷, Liemin Zhou¹¹, Guanxun Cheng¹², Xinlu Wang¹⁸, Pengcheng Ran¹⁹, Lu Wang²⁰, Kun Sun²¹, Ying Han^{1

9

14

22

23

24}, Yihui Guan², Kaj Blennow^{25

26

27

28}, Fang Xie²⁹, Tengfei Guo^{30

31

32}

Affiliations

¹ Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China.
² Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China.
³ Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.
⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
⁶ Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong Special Administrative Region, China.
⁷ Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁸ Westlake and Shenzhen Medical Academy of Research and Translation PhD Program, Westlake University, Hangzhou, China.
⁹ Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.
¹⁰ Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, China.
¹¹ Neurology Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
¹² Department of Medical Imaging, Peking University Shenzhen Hospital, Shenzhen, China.
¹³ School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
¹⁴ School of Biomedical Engineering, Hainan University, Haikou, China.
¹⁵ School of Pharmaceutical Sciences, Shenzhen Campus of Sun Yat-sen University, Shenzhen, China.
¹⁶ Department of Neurology, Shenzhen Guangming District People's Hospital, Shenzhen, China.
¹⁷ Department of Medical Imaging, Shenzhen Guangming District People's Hospital, Shenzhen, China.
¹⁸ Department of Nuclear Medicine, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
¹⁹ Department of Nuclear Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
²⁰ Department of Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.
²¹ Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China.
²² Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China.
²³ National Clinical Research Center for Geriatric Diseases, Beijing, China.
²⁴ The Central Hospital of Karamay, Xinjiang, China.
²⁵ Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden. kaj.blennow@neuro.gu.se.
²⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. kaj.blennow@neuro.gu.se.
²⁷ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France. kaj.blennow@neuro.gu.se.
²⁸ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, China. kaj.blennow@neuro.gu.se.
²⁹ Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China. fangxie@fudan.edu.cn.
³⁰ Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen, China. tengfei.guo@szbl.ac.cn.
³¹ Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen, China. tengfei.guo@szbl.ac.cn.
³² Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Peking University, Shenzhen, China. tengfei.guo@szbl.ac.cn.

^# Contributed equally.

PMID: 40550877
DOI: 10.1038/s43587-025-00904-3

Abstract

Over 20% of patients with Alzheimer's disease (AD) worldwide are Chinese, although the efficacy of existing blood-based measures of AD biomarkers is largely unknown in Asian cohorts. Here we explored how plasma tau biomarkers correlated with cross-sectional and longitudinal AD-related outcomes and their diagnostic performance in 1,085 participants from three independent studies, including two Chinese cohorts, Greater-Bay-Area Healthy Aging Brain Study (n = 425) and Huashan (n = 297), and the North American Alzheimer's Disease Neuroimaging Initiative cohort (n = 363). Plasma p-tau217 performed best in classifying Aβ-positron emission tomography (PET) and tau-PET positivity throughout the AD continuum and correlated with all AD-related outcomes. A two-cutoff approach suggested that participants with intermediate plasma p-tau217 levels experienced rapid accumulation of Aβ-PET and entorhinal tau-PET, as well as accelerated hypometabolism and cognitive decline. Increased plasma p-tau217 was also associated with rapid longitudinal changes in Aβ-PET, tau-PET and neurodegeneration. These results suggest that plasma p-tau217 is superior in detecting multiple aspects of AD-related pathological changes and tracking disease progression.

Abstract

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