{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:37:05Z","timestamp":1754145425737,"version":"3.41.2"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82130036"],"award-info":[{"award-number":["82130036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 allele is the most important genetic risk factor for sporadic Alzheimer's disease (AD), yet its mechanisms in AD pathology and cognitive decline remain unclear. Using a sliding\u2010time window approach to directly quantify the instantaneous fluctuations of various local metrics based on continuous time series and calculate voxel\u2010wise concordance of these metrics, we explored the impact of <jats:italic>APOE<\/jats:italic> \u03b54 on dynamic local brain activity and functional integration in AD, and its interrelations with plasma biomarkers and cognition. Results showed that <jats:italic>APOE<\/jats:italic> \u03b54 widely affected dALFF, dReHo, dGSCorr, and voxel\u2010wise concordance. For AD patients, <jats:italic>APOE<\/jats:italic> \u03b54 carriers uniquely exhibited correlations between dALFF in the right angular gyrus\/supramarginal gyrus and MoCA scores and orientation function, and between voxel\u2010wise concordance in the right caudate nucleus (CAU) and general cognition, attention, language function, orientation function, plasma A\u03b242. Critically, <jats:italic>APOE<\/jats:italic> \u03b54\u2010related altered voxel\u2010wise concordance in the right CAU mediated the relationship between plasma A\u03b2 and language cognition in AD. Moreover, the combined model incorporating dynamic metrics, plasma AD biomarkers, and demographic data effectively distinguished AD from NC (AUC\u2009=\u20090.94, sensitivity\u2009=\u200987.69%, specificity\u2009=\u200986.84%). In conclusion, the <jats:italic>APOE<\/jats:italic> \u03b54 allele might play a pivotal role in modulating brain dynamic functional activities in AD, which may contribute to the association between A\u03b2 pathology and cognitive decline. Our findings may provide imaging markers and targets for the diagnosis and treatment of AD.<\/jats:p>","DOI":"10.1002\/hbm.70269","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T10:15:07Z","timestamp":1752228907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of <scp><i>APOE<\/i><\/scp> \u03b54 Allele on Dynamic Local Spontaneous Brain Activity and Functional Integration in Alzheimer's Disease"],"prefix":"10.1002","volume":"46","author":[{"given":"Yi","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Neurology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-6122","authenticated-orcid":false,"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of 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