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Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Participants had dMRI and either beta\u2010amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed\n                      <jats:italic>post mortem<\/jats:italic>\n                      3D\u2010map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      There was higher isometric volume fraction in amyloid\u2010positive compared to amyloid\u2010negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and\n                      <jats:sup>18<\/jats:sup>\n                      F\u2010flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      Combining a\n                      <jats:italic>post mortem<\/jats:italic>\n                      atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>Highlights<\/jats:title>\n                      <jats:p>\n                        <jats:list list-type=\"bullet\">\n                          <jats:list-item>\n                            <jats:p>Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>dMRI measured microstructure in regions with high NFT.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Microstructural changes occur in medial temporal regions in preclinical disease.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>Microstructural changes occur in other typical Alzheimer's regions in later stages.<\/jats:p>\n                          <\/jats:list-item>\n                          <jats:list-item>\n                            <jats:p>\n                              Combining\n                              <jats:italic>post mortem<\/jats:italic>\n                              pathology atlases with in vivo MRI is a powerful framework.\n                            <\/jats:p>\n                          <\/jats:list-item>\n                        <\/jats:list>\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1002\/alz.13832","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T08:26:43Z","timestamp":1715761603000},"page":"4147-4158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-3976","authenticated-orcid":false,"given":"Christopher","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhitsu","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania 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