{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:29:46Z","timestamp":1792074586258,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG062483"],"award-info":[{"award-number":["R01 AG062483"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["K99\/R00 AG057797"],"award-info":[{"award-number":["K99\/R00 AG057797"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2024,12]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Blood\u2013brain barrier (BBB) dysfunction occurs in Alzheimer's disease (AD). Yet, the stage at which it appears along the AD time course and whether it contributes to neurodegeneration remain unclear.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Older adults (61 to 90 years) from cognitively normal (CN) to mildly cognitively impaired (CI), enriched for\n APOE<\/jats:italic>\n \ud835\udf004<\/jats:italic>\n and amyloid positivity, underwent dynamic contrast\u2010enhanced (DCE) magnetic resonance imaging (MRI) and diffusion MRI to measure BBB permeability and brain microstructure. Analysis of variance compared BBB permeability according to cognitive status, amyloid beta (A\u03b2), and\n APOE4<\/jats:italic>\n . Linear regressions assessed associations of BBB permeability with brain microstructure and interactions with A\u03b2 and\n APOE4<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n BBB permeability was elevated for\n APOE4<\/jats:italic>\n carriers across the cortical gray matter, with the strongest differences among CN amyloid\u2010negative individuals. Associations between entorhinal BBB permeability and microstructure interacted with A\u03b2 and\n APOE4<\/jats:italic>\n , with the strongest relationships in amyloid\u2010positive individuals and\n APOE4<\/jats:italic>\n carriers.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n APOE4<\/jats:italic>\n may drive widespread BBB dysfunction in preclinical AD, which may contribute to neurodegenerative changes early along the AD cascade.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Gray matter blood\u2013brain barrier (BBB) permeability is elevated for APOE4 carriers.<\/jats:p>\n <\/jats:list-item>\n \n APOE4\u2010related BBB breakdown appears in the absence of cognitive decline or amyloid.<\/jats:p>\n <\/jats:list-item>\n \n BBB leakage correlates with entorhinal cortex microstructural injury.<\/jats:p>\n <\/jats:list-item>\n \n Associations with microstructure are strongest for amyloid\u2010positive APOE4 carriers.<\/jats:p>\n <\/jats:list-item>\n 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