{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:47:50Z","timestamp":1794012470994,"version":"4.8.0"},"reference-count":75,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372036"],"award-info":[{"award-number":["82372036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["226\u20102023\u201000095"],"award-info":[{"award-number":["226\u20102023\u201000095"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The paramagnetic iron, diamagnetic amyloid beta (A\u03b2) plaques and their interaction are crucial in Alzheimer's disease (AD) pathogenesis, complicating non\u2010invasive magnetic resonance imaging for prodromal AD detection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We used a state\u2010of\u2010the\u2010art sub\u2010voxel quantitative susceptibility mapping method to simultaneously measure A\u03b2 and iron levels in\n                      <jats:italic>post mortem<\/jats:italic>\n                      human brains, validated by histology. Further transcriptomic analysis using Allen Human Brain Atlas elucidated the underlying biological processes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Regional increased paramagnetic and diamagnetic susceptibility were observed in medial prefrontal, medial parietal, and para\u2010hippocampal cortices associated with iron deposition (\n                      <jats:italic>R<\/jats:italic>\n                      \u00a0=\u00a00.836,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003) and A\u03b2 accumulation (\n                      <jats:italic>R<\/jats:italic>\n                      \u00a0=\u00a00.853,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.002) in AD brains. Higher levels of gene expression relating to cell cycle, post\u2010translational protein modifications, and cellular response to stress were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings provide quantitative insights into the variable vulnerability of cortical regions to higher levels of A\u03b2 aggregation, iron overload, and subsequent neurodegeneration, indicating changes preceding clinical symptoms.<\/jats:p>\n                  <\/jats:sec>\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>The vulnerability of distinct brain regions to amyloid beta (A\u03b2) and iron accumulation varies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Histological validation was performed on stained sections of ex\u2010vivo human brains.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Regional variations in susceptibility were linked to gene expression profiles.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Iron and A\u03b2 levels in ex\u2010vivo brains were simultaneously quantified.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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