Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we com...

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Detalles Bibliográficos
Autores: Ravikumar, Sadhana, Wisse, Laura E. M., Lim, Sydney, Ittyerah, Ranjit, Xie, Long, Bedard, Madigan L., Das, Sandhitsu R., Lee, Edward B., Tilsdall, M. Dylan, Prabhakaran, Karthink, Lane, Jacqueline, Detre, John A., Mizsei, Gabor, Trojanowski, John Q., Robinson, John l., Schuck, Theresa, Grossman, Murray, Artacho Pérula, Emilio, Íñiguez de Onzoño Martín, María Mercedes, Arroyo Jiménez, María del Mar, Muñoz López, Mónica, Molina Romero, Francisco Javier, Marcos Rabal, María del Pilar, Cebada Sánchez, Sandra, Delgado González, José Carlos, Rosa Prieto, Carlos de la, Córcoles Parada, Marta, Irwin, David J., Wolk, David A., Insausti Serrano, Ricardo, Yushkevich, Paul A.
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/34225
Acceso en línea:https://hdl.handle.net/10578/34225
Access Level:acceso abierto
Palabra clave:Alzheimer’s disease
Biomarkers
Co-morbidities
Ex vivo MRI
Neurodegeneration
Neurofibrillary tangles
Descripción
Sumario:Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer’s disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages. Introduction

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