Using CA1 rather than the whole hippocampus to capture tau-PET Braak stage II
Etienne Aumont1,2,3, Lydia Trudel1,2,3, Brandon J Hall1,2,3
1McGill University Research Centre for Studies in Aging, McGill University, 6825 Boulevard LaSalle, Verdun, Québec, H4H 1R3, Canada.
Summary
A new CA1-specific region of interest for tau-PET imaging improves Alzheimer disease staging. This method enhances biological accuracy and longitudinal consistency for early Braak stage II classification.
Area of Science:
- Neuroimaging
- Alzheimer's Disease Research
- Molecular Imaging
Background:
- Tau-PET imaging is crucial for in-vivo staging of Alzheimer disease (AD) pathology.
- Conventional whole-hippocampus analysis for tau accumulation is limited by heterogeneous subfields and off-target signals, impacting early detection sensitivity and specificity.
Purpose of the Study:
- To develop and validate a CA1-specific region of interest for tau-PET imaging to improve the classification of early Braak stage II Alzheimer disease pathology.
- To compare the biological plausibility and longitudinal stability of CA1-specific staging against conventional whole-hippocampus staging.
Main Methods:
- Cross-sectional and longitudinal analyses were performed on 456 participants in the TRIAD cohort and 497 in the ADNI cohort using tau-PET ([18F]MK-6240 or [18F]flortaucipir) and structural MRI.
- A CA1-specific region of interest was defined and compared with a whole-hippocampus approach for Braak stage II classification.
- Outcomes assessed included Braak stage concordance, longitudinal stability, tau-PET progression, and biological plausibility via amyloid-PET burden and extrahippocampal tau signal.
Main Results:
- Early hippocampal tau-PET signal was predominantly localized to the anterior CA1 subfield.
- Whole-hippocampus measures were more susceptible to off-target signals, such as choroid plexus contamination.
- CA1-based Braak stage II classification demonstrated higher amyloid-PET burden, more consistent tau accumulation in Braak stage III regions, and improved longitudinal stability with fewer discordant classifications and regressions.
Conclusions:
- CA1-specific tau-PET quantification enhances the biological plausibility and longitudinal consistency of Braak stage II classification in Alzheimer disease.
- This targeted approach mitigates off-target contamination and improves characterization of early tau pathology compared to whole-hippocampus methods.
- The CA1-specific method shows promise for improving early AD characterization and participant selection in clinical trials targeting preclinical tau accumulation.
