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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.<\/jats:p>","DOI":"10.1186\/s40478-021-01275-7","type":"journal-article","created":{"date-parts":[[2021,10,24]],"date-time":"2021-10-24T15:02:37Z","timestamp":1635087757000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-4731","authenticated-orcid":false,"given":"Sadhana","family":"Ravikumar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E. 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Where possible, pre-consent during life and, in all cases, next-of-kin consent at death was given.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have reviewed the contents of the manuscript being submitted, approved of its contents and validated the accuracy of the data and consented to publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"D.A.W has received grant support from Merck, Biogen, and Eli Lilly\/Avid. D.A.W received consultation fees from Neuronix and is on the DSMB for a clinical trial run by Functional Neuromodulation. L.X. received personal consultation fees from Galileo CDS, Inc. J.Q.T. may accrue revenue in the future on patents submitted by the University of Pennsylvania wherein he is co-Inventor and he received revenue from the sale of Avid to Eli Lily as co-inventor on imaging related patents submitted by the University of Pennsylvania.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"173"}}