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Plasma tau biomarkers for biological staging of Alzheimer’s disease

Montoliu-Gaya, Laia ; Salvadó, Gemma LU ; Therriault, Joseph ; Nilsson, Johanna ; Janelidze, Shorena LU ; Weiner, Sophia ; Ashton, Nicholas J. ; Benedet, Andrea L. LU ; Rahmouni, Nesrine and Lantero-Rodriguez, Juan , et al. (2025) In Nature Aging
Abstract

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... (More)

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.

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publication status
epub
subject
in
Nature Aging
publisher
Springer
external identifiers
  • scopus:105013803096
  • pmid:40847200
DOI
10.1038/s43587-025-00951-w
language
English
LU publication?
yes
id
bef4612e-b128-4850-9556-8130e9552062
date added to LUP
2025-11-17 14:57:16
date last changed
2025-11-18 03:22:58
@article{bef4612e-b128-4850-9556-8130e9552062,
  abstract     = {{<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 (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 (&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>}},
  author       = {{Montoliu-Gaya, Laia and Salvadó, Gemma and Therriault, Joseph and Nilsson, Johanna and Janelidze, Shorena and Weiner, Sophia and Ashton, Nicholas J. and Benedet, Andrea L. and Rahmouni, Nesrine and Lantero-Rodriguez, Juan and Mattsson-Carlgren, Niklas and Palmqvist, Sebastian and Brinkmalm, Gunnar and Stomrud, Erik and Zetterberg, Henrik and Gobom, Johan and Rosa-Neto, Pedro and Blennow, Kaj and Hansson, Oskar}},
  language     = {{eng}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{Plasma tau biomarkers for biological staging of Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1038/s43587-025-00951-w}},
  doi          = {{10.1038/s43587-025-00951-w}},
  year         = {{2025}},
}