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

Ourcurrentunderstanding ofthespreadandneurodegenerativeeffectsoftau 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 convention...

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Bibliographic Details
Authors: Ravikumar, Sadhana, Denning, Amanda E., Lim, Sydney, Chung, Eunice, Sadeghpour, Niyousha, Ittyerah, Ranjit, Wisse, Laura E. M., Das, Sandhitsu R., Xie, Long, Robinson, John L., Schuck, Theresa, Lee, Edward B., Detre, John A., Tisdall, M. Dylan, Prabhakaran, Karthik, Mizsei, Gabor, Íñiguez de Onzoño Martín, María Mercedes, Arroyo Jiménez, María del Mar, Muñoz López, Mónica, Marcos Rabal, María del Pilar, Cebada Sánchez, Sandra, Delgado González, José Carlos, Rosa Prieto, Carlos de la, Irwin, David J., Wolk, David A, Insausti Serrano, Ricardo, Yushkevich, Paul A.
Format: article
Publication Date:2024
Country:España
Institution:Universidad de Castilla-La Mancha
Repository:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/45042
Online Access:https://doi.org/10.1038/s41467-024-49205-0
https://www.nature.com/articles/s41467-024-49205-0.pdf
https://hdl.handle.net/10578/45042
Access Level:Open access
Keyword:Alzheimer’s disease
Biomarkers
Histological imaging
Medial temporal lobe
Neurodegeneration
Neurofibrillary tangles
Tau pathology
Description
Summary:Ourcurrentunderstanding ofthespreadandneurodegenerativeeffectsoftau 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 highresolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that canbeusedtoinformfutureinvivoneuroimagingstudies.Averagemapsshow 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.

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