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<p>A blood biomarker-based staging system for Alzheimer’s disease (AD) could improve the diagnosis, prognosis and identification of individuals most likely to benefit from specific therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (<i>n</i> = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specific tau species became abnormal at different points along the disease continuum. Based on these findings, we developed a data-driven, blood-based staging model that demonstrated strong consistency across cohorts (&gt;85% agreement in ≥90% initializations) and reflected changes in other AD biomarkers. These plasma-based stages were associated with clinical diagnoses, positron emission tomography-based stages and distinct patterns of longitudinal disease progression, including Aβ- and tau-positron emission tomography uptake, atrophy and cognitive decline. This study highlights the potential of tau blood-based biomarkers for biological staging in AD, offering a scalable tool for tracking disease progression and guiding clinical decisions.</p>

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Plasma tau biomarkers for biological staging of Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月22日

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  • Laia Montoliu-Gaya,
  • Gemma Salvadó,
  • Joseph Therriault,
  • Johanna Nilsson,
  • Shorena Janelidze,
  • Sophia Weiner,
  • Nicholas J. Ashton,
  • Andrea L. Benedet,
  • Nesrine Rahmouni,
  • Juan Lantero-Rodriguez,
  • Niklas Mattsson-Carlgren,
  • Sebastian Palmqvist,
  • Gunnar Brinkmalm,
  • Erik Stomrud,
  • Henrik Zetterberg,
  • Johan Gobom,
  • Pedro Rosa-Neto,
  • Kaj Blennow,
  • Oskar Hansson

摘要

A blood biomarker-based staging system for Alzheimer’s disease (AD) could improve the diagnosis, prognosis and identification of individuals most likely to benefit from specific therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (n = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specific tau species became abnormal at different points along the disease continuum. Based on these findings, we developed a data-driven, blood-based staging model that demonstrated strong consistency across cohorts (>85% agreement in ≥90% initializations) and reflected changes in other AD biomarkers. These plasma-based stages were associated with clinical diagnoses, positron emission tomography-based stages and distinct patterns of longitudinal disease progression, including Aβ- and tau-positron emission tomography uptake, atrophy and cognitive decline. This study highlights the potential of tau blood-based biomarkers for biological staging in AD, offering a scalable tool for tracking disease progression and guiding clinical decisions.