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We examined whole-brain associations between cortical thickness, cortical volume, GM density, tau, β-amyloid, and APOE ε4 genotype in MCI, assessing the impact of β-amyloid and APOE ε4 on the spatial relationship between atrophy measures and tau using a large-scale cross-correlation approach with SVD.

Key findings:

  • Cortical thinning, volume loss, and GM density reduction in MCI were not associated with APOE ε4 genotype.
  • Tau had a stronger association with brain atrophy measures than β-amyloid.
  • The relationship between tau and atrophy measures remained spatially consistent even after adjusting for β-amyloid.

This study is the first to analyze whole-brain atrophy patterns in relation to tau and β-amyloid using a network-based approach. Findings suggest that entorhinal tau accumulation and entorhinal cortical atrophy are key markers of cognitive decline.

Beta-amyloid PET, Tau PET and Cortical Thickness Images
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We have explored whole brain associations between cortical thickness, cortical volume, GM density, tau, β-amyloid and APOE ε4 genotype in a sample of MCI subjects. Our analysis assessed the impact of β-amyloid and APOE ε4 genotype on the spatial relationship between atrophy measures and tau.

To our knowledge, this study is the first to relate different structural atrophy measures with tau and β-amyloid from a whole brain network perspective that accounts for distributed-to-distributed patterns of cross-correlation. Our results highlight that the confluence of elevated entorhinal tau and entorhinal cortical atrophy is a useful hallmark of cognitive deterioration.

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