Nature communications · 2024
Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer's disease.
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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, de Onzono Martin Maria Mercedes Iñiguez, Arroyo Jiménez Maria Del Mar, Mũnoz Monica, Marcos Rabal Maria Del Pilar, Cebada Sánchez Sandra, Delgado González José Carlos, de la Rosa Prieto Carlos, Irwin David J, Wolk David A, Insausti Ricardo, Yushkevich Paul A
Аннотация
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.