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Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease

Author

Listed:
  • Sadhana Ravikumar

    (University of Pennsylvania)

  • Amanda E. Denning

    (University of Pennsylvania)

  • Sydney Lim

    (University of Pennsylvania)

  • Eunice Chung

    (University of Pennsylvania)

  • Niyousha Sadeghpour

    (University of Pennsylvania)

  • Ranjit Ittyerah

    (University of Pennsylvania)

  • Laura E. M. Wisse

    (Lund University)

  • Sandhitsu R. Das

    (University of Pennsylvania)

  • Long Xie

    (University of Pennsylvania)

  • John L. Robinson

    (University of Pennsylvania)

  • Theresa Schuck

    (University of Pennsylvania)

  • Edward B. Lee

    (University of Pennsylvania)

  • John A. Detre

    (University of Pennsylvania)

  • M. Dylan Tisdall

    (University of Pennsylvania)

  • Karthik Prabhakaran

    (University of Pennsylvania)

  • Gabor Mizsei

    (University of Pennsylvania)

  • Maria Mercedes Iñiguez Onzono Martin

    (University of Castilla La Mancha)

  • Maria del Mar Arroyo Jiménez

    (University of Castilla La Mancha)

  • Monica Mũnoz

    (University of Castilla La Mancha)

  • Maria del Pilar Marcos Rabal

    (University of Castilla La Mancha)

  • Sandra Cebada Sánchez

    (University of Castilla La Mancha)

  • José Carlos Delgado González

    (University of Castilla La Mancha)

  • Carlos Rosa Prieto

    (University of Castilla La Mancha)

  • David J. Irwin

    (University of Pennsylvania)

  • David A. Wolk

    (University of Pennsylvania)

  • Ricardo Insausti

    (University of Castilla La Mancha)

  • Paul A. Yushkevich

    (University of Pennsylvania)

Abstract

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer’s Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.

Suggested Citation

  • Sadhana Ravikumar & Amanda E. Denning & Sydney Lim & Eunice Chung & Niyousha Sadeghpour & Ranjit Ittyerah & Laura E. M. Wisse & Sandhitsu R. Das & Long Xie & John L. Robinson & Theresa Schuck & Edward, 2024. "Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49205-0
    DOI: 10.1038/s41467-024-49205-0
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    References listed on IDEAS

    as
    1. Nicolai Franzmeier & Julia Neitzel & Anna Rubinski & Ruben Smith & Olof Strandberg & Rik Ossenkoppele & Oskar Hansson & Michael Ewers, 2020. "Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
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