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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Detalhes bibliográficos
Autores: 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.
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/45042
Acesso em linha: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:acceso abierto
Palavra-chave:Alzheimer’s disease
Biomarkers
Histological imaging
Medial temporal lobe
Neurodegeneration
Neurofibrillary tangles
Tau pathology
Descrição
Resumo: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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