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White matter fractional anisotropy decreases precede hyperintensities in Alzheimer's disease

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机构： [1]Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China. [2]School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China. [3]Department of Medical Imaging, Shenzhen Guangming District People's Hospital, Shenzhen 518000, China. [4]Department of Medical Imaging, Peking University Shenzhen Hospital, Shenzhen 518036, China. [5]Neurology Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518000, China. [6]School of Electronic and Information Engineering, Harbin Institute of Technology (Shenzhen), Shenzhen 518055, China. [7]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. [8]Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong 999077, China. [9]School of Biomedical Engineering, Hainan University, Haikou 570228, China. [10]Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China [11]Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

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The associations of β-amyloid (Aβ) and tau deposition with white matter (WM) degeneration in Alzheimer's disease (AD) remain inadequately elucidated. We investigate baseline and longitudinal changes of microstructural fractional anisotropy (FA) and macrostructural white matter hyperintensities (WMHs) and their relationships with Aβ and tau positron emission tomography (PET) and vascular risk factors in different Aβ/tau stages defined by PET imaging. Lower levels and faster decline rates of FA occur in the AD continuum, particularly in tau-positive individuals. Tau-related FA decreases are correlated with higher burden and faster increase rates of WMH but not vice versa. These results are substantially replicated in an independent cohort. This study suggests that tau is tightly linked with microstructural WM degeneration, appearing earlier than macrostructural WM alteration in AD. Our findings provide valuable insights for detecting and monitoring early WM degeneration in AD, highlighting the importance of targeting tau clearance to maintain healthy WM integrity.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.

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出版当年[2025]版：

大类 | 1 区

医学

小类 | 1 区医学：研究与实验 2 区细胞生物学

最新[2025]版：

大类 | 1 区

医学

小类 | 1 区医学：研究与实验 2 区细胞生物学

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第一作者机构： [1]Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China.

通讯作者：

通讯机构： [1]Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, Shenzhen 518132, China. [10]Institute of Biomedical Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China [11]Institute of Biomedical Engineering, Peking University Shenzhen Graduate School, Shenzhen 518055, China.

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