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

• Published in: Acta neuropathologica communications Vol. 9; no. 1; p. 173
• Main Authors: Ravikumar, Sadhana, Wisse, Laura E M, Lim, Sydney, Ittyerah, Ranjit, Xie, Long, Bedard, Madigan L, Das, Sandhitsu R, Lee, Edward B, Tisdall, M Dylan, Prabhakaran, Karthik, Lane, Jacqueline, Detre, John A, Mizsei, Gabor, Trojanowski, John Q, Robinson, John L, Schuck, Theresa, Grossman, Murray, Artacho-Pérula, Emilio, de Onzoño Martin, Maria Mercedes Iñiguez, Del Mar Arroyo Jiménez, María, Muñoz, Monica, Romero, Francisco Javier Molina, Del Pilar Marcos Rabal, Maria, Sánchez, Sandra Cebada, González, José Carlos Delgado, de la Rosa Prieto, Carlos, Parada, Marta Córcoles, Irwin, David J, Wolk, David A, Insausti, Ricardo, Yushkevich, Paul A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24-10-2021; BioMed Central; BMC
• Subjects: Adult; Advertising executives; Aged; Aged, 80 and over; Alzheimer's disease; Atlases as Topic; Basic Medicine; Biomarkers; Co-morbidities; Comparative analysis; Ex vivo MRI; Female; Humans; Imaging, Three-Dimensional - methods; Magnetic Resonance Imaging; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; Neurodegeneration; Neurofibrillary tangles; Neurofibrillary Tangles - pathology; Neuroimaging - methods; Neurosciences; Neurovetenskaper; Pathology; Physiological aspects; Protein binding; Ratings & rankings; tau Proteins; Temporal Lobe - diagnostic imaging; Temporal Lobe - pathology; Biomarkers; Ex vivo MRI; Neurofibrillary tangles; Alzheimer’s disease; Co-morbidities; Neurodegeneration
• DOI: 10.1186/s40478-021-01275-7
• EISSN: 2051-5960

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.