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<p>Recently, conceptual systems for the in vivo staging of Alzheimer’s disease (AD) using fluid biomarkers have been suggested. Thus, it is important to assess whether available fluid biomarkers can successfully stage AD into clinically and biologically relevant categories. In the TRIAD cohort, we explored whether p-tau217, p-tau205 and NTA-tau (biomarkers of early, intermediate and late AD pathology, respectively) have potential for biofluid-based staging in cerebrospinal fluid (CSF; <i>n</i> = 219) and plasma (<i>n</i> = 150), and compared them in a paired CSF and plasma subset (<i>n</i> = 76). Our findings suggest a good concordance between biofluid staging and underlying pathology when classifying amyloid-positivity into three categories based on neurofibrillary pathology: minimal/non-existent (p-tau217 positive), early-to-intermediate (p-tau217 and p-tau205 positivity), and advanced tau tangle deposition (p-tau217, p-tau205 and NTA-tau positive), as indexed by tau-PET. Discordant cases accounted for 4.6% and 13.3% of all CSF and plasma measurements respectively (9.2% and 11.8% in paired samples). Notably, CSF- and plasma-based staging matched one another in 61.7% of the cases, while approximately 32% of the remaining participants were one to three biofluid stages higher in CSF as compared to plasma. Overall, these exploratory results suggest that biofluid staging of AD holds potential for offering valuable insights into underlying AD hallmarks and disease severity. However, its applicability beyond molecular characterization at research settings has yet to be demonstrated.</p>

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Biofluid-based staging of Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月17日

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  • Juan Lantero-Rodriguez,
  • Laia Montoliu-Gaya,
  • Nicholas J. Ashton,
  • Ilaria Pola,
  • Joseph Therriault,
  • Nesrine Rahmouni,
  • Wagner S. Brum,
  • Stijn Servaes,
  • Jenna Stevenson,
  • Guglielmo Di Molfetta,
  • Burak Arslan,
  • Jesse Klostranec,
  • Paolo Vitali,
  • Maxime Montembeault,
  • Serge Gauthier,
  • Cecile Tissot,
  • Arthur C. Macedo,
  • Tharick A. Pascoal,
  • Andreas Jeromin,
  • Johan Gobom,
  • Kaj Blennow,
  • Henrik Zetterberg,
  • Pedro Rosa-Neto,
  • Andrea L. Benedet

摘要

Recently, conceptual systems for the in vivo staging of Alzheimer’s disease (AD) using fluid biomarkers have been suggested. Thus, it is important to assess whether available fluid biomarkers can successfully stage AD into clinically and biologically relevant categories. In the TRIAD cohort, we explored whether p-tau217, p-tau205 and NTA-tau (biomarkers of early, intermediate and late AD pathology, respectively) have potential for biofluid-based staging in cerebrospinal fluid (CSF; n = 219) and plasma (n = 150), and compared them in a paired CSF and plasma subset (n = 76). Our findings suggest a good concordance between biofluid staging and underlying pathology when classifying amyloid-positivity into three categories based on neurofibrillary pathology: minimal/non-existent (p-tau217 positive), early-to-intermediate (p-tau217 and p-tau205 positivity), and advanced tau tangle deposition (p-tau217, p-tau205 and NTA-tau positive), as indexed by tau-PET. Discordant cases accounted for 4.6% and 13.3% of all CSF and plasma measurements respectively (9.2% and 11.8% in paired samples). Notably, CSF- and plasma-based staging matched one another in 61.7% of the cases, while approximately 32% of the remaining participants were one to three biofluid stages higher in CSF as compared to plasma. Overall, these exploratory results suggest that biofluid staging of AD holds potential for offering valuable insights into underlying AD hallmarks and disease severity. However, its applicability beyond molecular characterization at research settings has yet to be demonstrated.