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

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 B. Lee, John A. Detre, M. Dylan Tisdall, Karthik Prabhakaran, Gabor Mizsei, Maria Mercedes Iñiguez Onzono Martin, Maria del Mar Arroyo Jiménez, Monica Mũnoz, Maria del Pilar Marcos Rabal, Sandra Cebada Sánchez, José Carlos Delgado González, Carlos Rosa Prieto, David J. Irwin, David A. Wolk, Ricardo Insausti and Paul A. Yushkevich ()
Additional contact information
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

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49205-0

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DOI: 10.1038/s41467-024-49205-0

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