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Purpose <p>Tau-PET enables in-vivo staging of Alzheimer disease (AD) pathology, including early Braak stage II involvement of the hippocampus. Conventional whole-hippocampus definitions combine heterogeneous subfields and are susceptible to off-target signal that varies across tracers, limiting sensitivity, specificity, and longitudinal interpretability of early tau accumulation.</p> Methods <p>Cross-sectional and longitudinal analyses were conducted in the TRIAD (<i>N</i> = 456) and the ADNI (<i>N</i> = 497) observational cohorts with tau-PET with [<sup>18</sup>F]MK-6240 or [<sup>18</sup>F]flortaucipir and structural MRI. A CA1-specific Braak stage II region of interest was compared with a whole-hippocampus approach. Outcomes included Braak stage concordance, longitudinal stability, tau-PET progression, and biological plausibility assessed by amyloid-PET burden and extrahippocampal tau signal.</p> Results <p>Spatial analyses localised early hippocampal tau-PET signal predominantly to the anterior CA1. Whole-hippocampus measures were more frequently influenced by off-target signal consistent with choroid plexus contamination. Participants classified as CA1-based Braak stage II showed higher amyloid-PET burden, more consistent tau accumulation in the Braak stage III region, and more stable longitudinal progression. CA1-based staging yielded fewer discordant classifications and fewer stage regressions at follow-up.</p> Conclusion <p>CA1-specific tau-PET quantification improves biological plausibility and longitudinal consistency of Braak stage II classification by targeting the hippocampal subfield most vulnerable to early tau pathology and mitigating off-target contamination. CA1-based Braak stage II participants showed greater coherence with the biological framework of AD than those staged using the whole hippocampus. Applicable to available PET resolution, this approach may enhance characterisation of early AD and support participant selection in trials targeting preclinical tau accumulation.</p>

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Using CA1 rather than the whole hippocampus to capture tau-PET Braak stage II

  • 期刊论文

  • 发表日期：

    2026年7月15日

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  • Etienne Aumont,
  • Lydia Trudel,
  • Brandon J. Hall,
  • Tevy Chan,
  • Seyyed Ali Hosseini,
  • Arthur C. Macedo,
  • Joseph Therriault,
  • Jaime Fernandez Arias,
  • Aurélie Lebrun,
  • Delphine Oliva-Lopez,
  • Nesrine Rahmouni,
  • Gleb Bezgin,
  • Jenna Stevenson,
  • Stijn Servaes,
  • Vladimir Fonov,
  • Chris Hsiao,
  • Robert Hopewell,
  • Paolo Vitali,
  • Jesse Klostranec,
  • Maxime Montembeault,
  • Yasser Iturria-Medina,
  • Suzanne L. Baker,
  • Serge Gauthier,
  • Pedro Rosa-Neto

摘要

Purpose

Tau-PET enables in-vivo staging of Alzheimer disease (AD) pathology, including early Braak stage II involvement of the hippocampus. Conventional whole-hippocampus definitions combine heterogeneous subfields and are susceptible to off-target signal that varies across tracers, limiting sensitivity, specificity, and longitudinal interpretability of early tau accumulation.

Methods

Cross-sectional and longitudinal analyses were conducted in the TRIAD (N = 456) and the ADNI (N = 497) observational cohorts with tau-PET with [18F]MK-6240 or [18F]flortaucipir and structural MRI. A CA1-specific Braak stage II region of interest was compared with a whole-hippocampus approach. Outcomes included Braak stage concordance, longitudinal stability, tau-PET progression, and biological plausibility assessed by amyloid-PET burden and extrahippocampal tau signal.

Results

Spatial analyses localised early hippocampal tau-PET signal predominantly to the anterior CA1. Whole-hippocampus measures were more frequently influenced by off-target signal consistent with choroid plexus contamination. Participants classified as CA1-based Braak stage II showed higher amyloid-PET burden, more consistent tau accumulation in the Braak stage III region, and more stable longitudinal progression. CA1-based staging yielded fewer discordant classifications and fewer stage regressions at follow-up.

Conclusion

CA1-specific tau-PET quantification improves biological plausibility and longitudinal consistency of Braak stage II classification by targeting the hippocampal subfield most vulnerable to early tau pathology and mitigating off-target contamination. CA1-based Braak stage II participants showed greater coherence with the biological framework of AD than those staged using the whole hippocampus. Applicable to available PET resolution, this approach may enhance characterisation of early AD and support participant selection in trials targeting preclinical tau accumulation.