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Purpose <p>The 2024 Alzheimer’s Association Workgroup research framework designates tau proteinopathy (T<sub>2</sub>) as a key element for Alzheimer’s disease (AD) staging, but optimal staging approaches have yet to be determined. Here, we compared visual and quantitative tau-PET–based Braak staging as candidate strategies to implement T<sub>2</sub> biological staging in vivo.</p> Methods <p>We included 140 participants from the TRIAD cohort who underwent [<sup>1</sup>⁸F]MK6240 tau-PET. Quantitative Braak staging (qBraak) was derived from regional SUVR thresholds, whereas visual Braak staging (vBraak) was independently performed by three nuclear medicine physicians using an adapted interpretation algorithm. Inter-rater and inter-method agreement were assessed using Cohen’s and Fleiss’ κ statistics. Associations with clinical severity, cortical thickness, plasma pTau217, and cortical tau extent were examined. Diagnostic performance for identifying amyloid-positive cognitively impaired individuals was evaluated.</p> Results <p>vBraak demonstrated substantial to nearly perfect inter-rater agreement (κ = 0.65–0.93). Agreement between vBraak and qBraak was moderate when stages were treated categorically (κ = 0.51), but substantial when their ordinal nature was considered (weighted κ up to 0.73). Both strategies showed comparable associations with clinical severity and neurodegeneration. vBraak was more sensitive to amyloid-β–positive cognitive impairment and identified intermediate-stage involvement at lower global tau extent. Visual-quantitative discordant cases were primarily attributable to off-target binding or spatially heterogeneous tau patterns.</p> Conclusion <p>Both vBraak and qBraak staging provide complementary and largely concordant approaches for operationalizing T<sub>2</sub> staging. Quantitative methods enable scalable, group-level analyses, whereas visual assessment remains essential for identifying atypical tau patterns and informing clinically relevant decision-making.</p>

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Visual versus quantitative tau-PET Braak staging in Alzheimer’s disease using [18F]MK6240

  • 期刊论文

  • 发表日期：

    2026年5月22日

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  • Arthur C. Macedo,
  • Karine Provost,
  • Jean-Paul Soucy,
  • Arlette Haeger,
  • Joseph Therriault,
  • Lydia Trudel,
  • Nesrine Rahmouni,
  • Jaime Fernandez-Arias,
  • Étienne Aumont,
  • Aurélie Lebrun,
  • Tevy Chan,
  • Seyyed Ali Hosseini,
  • Gleb Bezgin,
  • Cécile Tissot,
  • Stijn Servaes,
  • Brandon Hall,
  • Jenna Stevenson,
  • Robert Hopewell,
  • Chris Hung-Hsin Hsiao,
  • Gallen Triana-Baltzer,
  • Hartmuth C. Kolb,
  • Andréa L. Benedet,
  • Gassan Massarweh,
  • Jesse Klostranec,
  • Paolo Vitali,
  • Tharick A. Pascoal,
  • Pedro Rosa-Neto

摘要

Purpose

The 2024 Alzheimer’s Association Workgroup research framework designates tau proteinopathy (T2) as a key element for Alzheimer’s disease (AD) staging, but optimal staging approaches have yet to be determined. Here, we compared visual and quantitative tau-PET–based Braak staging as candidate strategies to implement T2 biological staging in vivo.

Methods

We included 140 participants from the TRIAD cohort who underwent [1⁸F]MK6240 tau-PET. Quantitative Braak staging (qBraak) was derived from regional SUVR thresholds, whereas visual Braak staging (vBraak) was independently performed by three nuclear medicine physicians using an adapted interpretation algorithm. Inter-rater and inter-method agreement were assessed using Cohen’s and Fleiss’ κ statistics. Associations with clinical severity, cortical thickness, plasma pTau217, and cortical tau extent were examined. Diagnostic performance for identifying amyloid-positive cognitively impaired individuals was evaluated.

Results

vBraak demonstrated substantial to nearly perfect inter-rater agreement (κ = 0.65–0.93). Agreement between vBraak and qBraak was moderate when stages were treated categorically (κ = 0.51), but substantial when their ordinal nature was considered (weighted κ up to 0.73). Both strategies showed comparable associations with clinical severity and neurodegeneration. vBraak was more sensitive to amyloid-β–positive cognitive impairment and identified intermediate-stage involvement at lower global tau extent. Visual-quantitative discordant cases were primarily attributable to off-target binding or spatially heterogeneous tau patterns.

Conclusion

Both vBraak and qBraak staging provide complementary and largely concordant approaches for operationalizing T2 staging. Quantitative methods enable scalable, group-level analyses, whereas visual assessment remains essential for identifying atypical tau patterns and informing clinically relevant decision-making.