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Microstructural pattern of the anterior part of human hippocampus, however, has not been well elucidated with ex vivo dMRI, either in normal or disease conditions. The present study collected high\u2010resolution (0.1\u2009mm isotropic) dMRI of post\u2010mortem anterior hippocampal tissues from four Alzheimer's diseases (AD), three primary age\u2010related tauopathy (PART), and three healthy control (HC) brains on a 14.1\u00a0T spectrometer. We evaluated how AD affected dMRI\u2010based microstructural features in different layers and subfields of anterior hippocampus. In the HC samples, we found higher anisotropy, lower diffusivity, and more streamlines in the layers within cornu ammonis (CA) than those within dentate gyrus (DG). Comparisons between disease groups showed that (1) anisotropy measurements in the CA layers of AD, especially stratum lacunosum (SL) and stratum radiatum (SR), had higher regional variability than the other two groups; (2) streamline density in the DG layers showed a gradually increased variance from HC to PART to AD; (3) AD also showed the higher variability in terms of inter\u2010layer connectivity than HC or PART. Moreover, voxelwise correlation analysis between the coregistered dMRI and histopathology images revealed significant correlations between dMRI measurements and the contents of amyloid beta (A\u03b2)\/tau protein in specific layers of AD samples. These findings may reflect layer\u2010specific microstructural characteristics in different hippocampal subfields at the mesoscopic resolution, which were associated with protein deposition in the anterior hippocampus of AD patients.<\/jats:p>","DOI":"10.1002\/hbm.26062","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T14:14:50Z","timestamp":1662128090000},"page":"458-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Layer\u2010specific microstructural patterns of anterior hippocampus in Alzheimer's disease with ex vivo diffusion <scp>MRI<\/scp> at 14.1\u00a0<scp>T<\/scp>"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-0430","authenticated-orcid":false,"given":"Zhiyong","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, 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