Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology
Year: 2021
Type: article
Study design: Observational Study
Abstract: 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.
Authors: Sadhana Ravikumar, Laura E. M. Wisse, Sydney Lim, Ranjit Ittyerah, Long Xie, Madigan L. Bedard, Sandhitsu R. Das, Edward B. Lee, M. Dylan Tisdall, Karthik Prabhakaran, Jacqueline Lane, John A. Detre, Gabor Mizsei, John Q. Trojanowski, John L. Robinson, Theresa Schuck, Murray Grossman, Emilio Artacho-Pérula, Maria Mercedes Iñiguez de Onzoño Martin, María del Mar Arroyo Jiménez, Monica Muñoz, Francisco Javier Molina Romero, Maria del Pilar Marcos Rabal, Sandra Cebada Sánchez, José Carlos Delgado González, Carlos de la Rosa Prieto, Marta Córcoles Parada, David J. Irwin, David A. Wolk, Ricardo Insausti, Paul A. Yushkevich
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,170
Funders: Foundation for the National Institutes of Health, Alzheimer's Association, University of Pennsylvania, Universidad de Castilla-La Mancha, National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering
Awards: G1236162799, G1263262031, G1310852075, G1635571750, G1672092672, G1734067475, G297470005, G3919444319, G4257815260, Alzheimer's Disease Core Center, Frontotemporal Dementias: Genotypes and Phenotypes, Adaptive Large-Scale Framework for Automatic Biomedical Image Segmentation, G504619356, Spreading Tau Pathology in Non-Amnestic Alzheimer's Disease, Penn Alzheimer's Disease Research Center (ADRC), Etiology and Progression of Suspected Non-Alzheimer’s Pathophysiology
OpenAlex ID: W3208880243