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<p>This longitudinal study including four independent cohorts assessed the spatiotemporal dynamics of tau extent and load changes in Alzheimer’s disease using tau positron emission tomography data from 2,459 participants, including 898 followed for up to 7 years. Regional standardized uptake value ratios indexed tau load, whereas the spatial extent of tauopathy (SEOT) (proportion of abnormal voxels) measured tau extent. We observed burden-dependent longitudinal dynamics of tau progression: SEOT showed greater sensitivity to increases over time in regions with low baseline tau burden, whereas the standardized uptake value ratio was more informative for tracking accumulation once regional burden was established. This pattern was consistent across Braak regions and cohorts and was reflected in differential associations with other Alzheimer’s disease severity markers. These findings refine models of tau propagation by suggesting that tau positron emission tomography changes may be differentially captured by extent-based and load-based metrics at different stages of disease progression, highlighting SEOT as a promising surrogate outcome for trials.</p>

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Spatiotemporal dynamics of tau extent and load increase in Alzheimer’s disease across four longitudinal cohorts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月14日

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  • Arthur C. Macedo,
  • Lydia Trudel,
  • Joseph Therriault,
  • Nesrine Rahmouni,
  • Étienne Aumont,
  • Gleb Bezgin,
  • Seyyed Ali Hosseini,
  • Cécile Tissot,
  • Tevy Chan,
  • Stijn Servaes,
  • Brandon Hall,
  • Yi-Ting Wang,
  • Kely Quispialaya-Socualaya,
  • Marcel S. Woo,
  • Jaime Fernandez-Arias,
  • Jenna Stevenson,
  • Yansheng Zheng,
  • Marina Pereira Gonçalves,
  • Firoza Z. Lussier,
  • João Pedro Ferrari-Souza,
  • Pamela C. L. Ferreira,
  • Bruna Bellaver,
  • Guilherme Povala,
  • Livia Silva do Amaral,
  • Gassan Massarweh,
  • Jean-Paul Soucy,
  • Karin L. Meeker,
  • Meredith N. Braskie,
  • Tobey J. Betthauser,
  • Bradley T. Christian,
  • Ramiro Eduardo Rea Reyes,
  • Jessica K. Caldwell,
  • Nicholas J. Ashton,
  • Thomas K. Karikari,
  • Henrik Zetterberg,
  • Kaj Blennow,
  • Eduardo R. Zimmer,
  • Andréa L. Benedet,
  • Sterling C. Johnson,
  • Tharick A. Pascoal,
  • Pedro Rosa-Neto

摘要

This longitudinal study including four independent cohorts assessed the spatiotemporal dynamics of tau extent and load changes in Alzheimer’s disease using tau positron emission tomography data from 2,459 participants, including 898 followed for up to 7 years. Regional standardized uptake value ratios indexed tau load, whereas the spatial extent of tauopathy (SEOT) (proportion of abnormal voxels) measured tau extent. We observed burden-dependent longitudinal dynamics of tau progression: SEOT showed greater sensitivity to increases over time in regions with low baseline tau burden, whereas the standardized uptake value ratio was more informative for tracking accumulation once regional burden was established. This pattern was consistent across Braak regions and cohorts and was reflected in differential associations with other Alzheimer’s disease severity markers. These findings refine models of tau propagation by suggesting that tau positron emission tomography changes may be differentially captured by extent-based and load-based metrics at different stages of disease progression, highlighting SEOT as a promising surrogate outcome for trials.