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Background <p>Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates.</p> Methods <p>To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions.</p> Results <p>Longitudinal and cross-sectional MCA in large aging cohort identified individual profiles (<i>N</i> = 753) expressing tau load in the entorhinal, limbic and neocortical regions. Using these profiles, we found neuropsychological and blood-based milestones of early and late disease stages. Finally, we also found evidence of rapid tau load increases and cognitive decline centered at the early-to-mid neocortical stages of Alzheimer’s disease.</p> Conclusions <p>Stage system based on tau load and spreading profiles across cortical areas provide a compelling framework for inferring pathophysiological prognosis in Alzheimer’s disease.</p>

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Tau profiling across Alzheimer’s disease staging reveals vulnerability to disease pathophysiology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月25日

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  • Gleb Bezgin,
  • Tharick A. Pascoal,
  • Joseph Therriault,
  • Firoza Z. Lussier,
  • Stijn Servaes,
  • Min Su Kang,
  • Mélissa Savard,
  • Cécile Tissot,
  • Jenna Stevenson,
  • Yi-Ting Wang,
  • Julie Ottoy,
  • Nesrine Rahmouni,
  • Jaime Fernandez-Arias,
  • Seyyed Ali Hosseini,
  • Étienne Aumont,
  • Brandon Hall,
  • Nina Margherita Poltronetti,
  • Vanessa Pallen,
  • Andréa Lessa Benedet,
  • Nicholas J. Ashton,
  • Kaj Blennow,
  • Henrik Zetterberg,
  • Thomas K. Karikari,
  • Tatsuhiro Terada,
  • Mira Chamoun,
  • Sulantha Mathotaarachchi,
  • Arthur Cassa Macedo,
  • Alyssa Stevenson,
  • Peter Kunach,
  • Gassan Massarweh,
  • Paolo Vitali,
  • Jean-Paul Soucy,
  • Yasser Iturria-Medina,
  • Serge Gauthier,
  • Pedro Rosa-Neto

摘要

Background

Inter-individual variability in tau topography challenges the propagation hypothesis of tau aggregates.

Methods

To address this gap, we propose the Manifold Component Analysis (MCA), for identifying pseudo-continuous profiles informed by the spatial continuity of stage regions.

Results

Longitudinal and cross-sectional MCA in large aging cohort identified individual profiles (N = 753) expressing tau load in the entorhinal, limbic and neocortical regions. Using these profiles, we found neuropsychological and blood-based milestones of early and late disease stages. Finally, we also found evidence of rapid tau load increases and cognitive decline centered at the early-to-mid neocortical stages of Alzheimer’s disease.

Conclusions

Stage system based on tau load and spreading profiles across cortical areas provide a compelling framework for inferring pathophysiological prognosis in Alzheimer’s disease.