{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:12:58Z","timestamp":1787019178187,"version":"build-2736575974"},"reference-count":46,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"he Nanjing Medical Science and Technology Development Key Projects","award":["ZKX23026"],"award-info":[{"award-number":["ZKX23026"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82471454"],"award-info":[{"award-number":["82471454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alzheimer's disease (AD) involves A\u03b2 and tau pathology, initiating years before symptoms. the apolipoprotein E \u03b54 allele (\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54) is the major genetic risk factor, influencing neurodegeneration and functional network disruption. This study investigates how\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 modulates the default mode network (DMN)'s hierarchical organization to accelerate cognitive decline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to elucidate how\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 accelerates AD pathological progression by altering the functional gradient hierarchy of DMN, and to evaluate the potential of DMN gradient abnormalities as an early diagnostic biomarker for AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We enrolled 271 participants, categorized by diagnosis and\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 status. All underwent neuropsychological assessment, plasma A\u03b2\n                      <jats:sub>42\/40<\/jats:sub>\n                      measurement, and resting-state functional MRI. DMN functional gradients were quantified using the BrainSpace toolbox. Statistical analyses included a 2\u2009\u00d7\u20092 factorial design, mediation analysis, and correlation testing with cognitive scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A significant Group\u2009\u00d7\u2009Genotype interaction was identified in the right inferior temporal gyrus (RITG). AD patients with\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 showed the most severe gradient attenuation, while non-carrier patients exhibited compensatory elevation. The RITG gradient correlated with multiple cognitive domains exclusively in\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 carriers. Altered connectivity between the left superior frontal gyrus (LSFG) and RITG mediated the effect of A\u03b2 burden on gradient disruption.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54 accelerates cognitive decline in AD by specifically disrupting the DMN functional gradient hierarchy, particularly within the right ITG. Amyloid-\u03b2 deposition contributes to macro-scale DMN topological disorganization by impairing LSFG-RITG functional connectivity. DMN functional gradient mapping provides a sensitive biomarker for early AD diagnosis and a novel target for\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      \u03b54-targeted interventions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251389965","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T17:17:24Z","timestamp":1761585444000},"page":"1726-1737","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Alzheimer's disease pathogenesis and the role of\n                    <i>APOE<\/i>\n                    \u03b54 in remodeling functional gradients of the default mode network"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5077-6330","authenticated-orcid":false,"given":"WenTing","family":"Song","sequence":"first","affiliation":[{"name":"Department 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