{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T16:41:11Z","timestamp":1771260071728,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"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":["U22A20294"],"award-info":[{"award-number":["U22A20294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Apolipoprotein E4 (APOE4) is a significant risk for both familial Alzheimer's disease (AD) and sporadic AD with elusive mechanisms. Previous studies mainly focused on the role of APOE4 in familial AD, with less attention to sporadic AD. Our previous study demonstrated that blood cell\u2010derived amyloid\u2010\u03b2 (A\u03b2) can enter the brain and induce AD\u2010like pathologies, providing a novel animal model to study sporadic AD to a certain extent. The impacts of APOE4 on Alzheimer\u2010like pathologies and cognitive deficits induced by blood\u2010derived A\u03b2 remain unknown. In the present study, we found that APOE4 prompted the entry of blood A\u03b2 into the brain. APOE4 recipient mice showed impaired integrity of the blood\u2013brain barrier and higher A\u03b2 levels in the brain after transplantation of bone marrow cells from APP\/PS1\u2022APOE4 mice. In addition, we observed that the APOE4 recipient mice displayed aggravated tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits at the age of 12\u2009months. Our study demonstrates that APOE4 is capable of facilitating the entry of blood\u2010derived A\u03b2 into the brain and enhancing the AD\u2010like pathologies triggered by blood\u2010derived A\u03b2. Our findings provide a possible way by which APOE4 elevates the risk of sporadic AD.<\/jats:p>","DOI":"10.1111\/acel.70205","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T14:20:57Z","timestamp":1756995657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>APOE4<\/scp> Exacerbates Alzheimer\u2010Like Pathologies and Cognitive Deficits Induced by Blood\u2010Derived A\u03b2 in a Mouse Model"],"prefix":"10.1111","volume":"24","author":[{"given":"Zhong\u2010Yuan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience Daping Hospital, Army Medical University (Third Military Medical University)  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience 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