{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:23:08Z","timestamp":1787242988279,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:00:00Z","timestamp":1760140800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006733","name":"Indiana University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG077829"],"award-info":[{"award-number":["R01AG077829"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG071281"],"award-info":[{"award-number":["R01AG071281"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AG072738"],"award-info":[{"award-number":["R21AG072738"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG074543"],"award-info":[{"award-number":["RF1AG074543"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["F31AG074673"],"award-info":[{"award-number":["F31AG074673"]}],"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":[[2025,10]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n \n The \u03b54 allele of the apolipoprotein E (\n APOE<\/jats:italic>\n ) gene is a risk factor for the development of Alzheimer's disease (AD).\n APOE4<\/jats:italic>\n isoform is associated with increased white matter lesions in humans. To identify the underlying mechanisms of white matter impairment associated with\n APOE4<\/jats:italic>\n , we investigated the effects of\n APOE4<\/jats:italic>\n and\n APOE3<\/jats:italic>\n on multiple readouts of the white matter microstructural integrity.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n Using magnetic resonance imaging and immunohistochemistry approaches, we analyzed white matter tracts in 5xFAD mice expressing\n APOE3<\/jats:italic>\n (5xFAD;\n APOE3<\/jats:italic>\n ) or\n APOE4<\/jats:italic>\n (5xFAD;\n APOE4<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n APOE4<\/jats:italic>\n significantly decreased fractional anisotropy, axial diffusivity, and neurite density index, while increasing radial diffusivity and isotropic volume fraction within major white matter tracts. Myelination was reduced in the corpus callosum of 5xFAD;\n APOE4<\/jats:italic>\n mice. Mechanistically,\n APOE4<\/jats:italic>\n reduced populations of mature and actively myelinating oligodendrocytes.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n Our results suggest that a decrease in the number of actively myelinating oligodendrocytes may explain myelin loss, leading to white matter impairments.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n A robust neurite orientation dispersion and density imaging (NODDI) approach to study the effect of apolipoprotein E (APOE) isoforms on the white matter in 5xFAD mice.<\/jats:p>\n <\/jats:list-item>\n \n APOE4 reduces neurite density and increases water accumulation in the white matter.<\/jats:p>\n <\/jats:list-item>\n \n APOE4 disrupts structural connectivity and reduces the betweenness centrality.<\/jats:p>\n <\/jats:list-item>\n \n APOE4 decreases the number of actively myelinating oligodendrocytes.<\/jats:p>\n <\/jats:list-item>\n \n A reduction in myelinating oligodendrocyte populations may lead to myelin loss.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70791","type":"journal-article","created":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:41:19Z","timestamp":1760193679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Apolipoprotein \u03b54 exacerbates white matter impairment in a mouse model of A\u03b2 amyloidosis by decreasing actively myelinating oligodendrocytes"],"prefix":"10.1002","volume":"21","author":[{"given":"Md Mamun","family":"Al\u2010Amin","sequence":"first","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byungwook","family":"Kim","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande","family":"Karahan","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mason D.","family":"Tate","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Medical Neuroscience Graduate Program Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam P.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta S.","family":"Puntambekar","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie J.","family":"Bissel","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce T.","family":"Lamb","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Medical Neuroscience Graduate Program Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nian","family":"Wang","sequence":"additional","affiliation":[{"name":"Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana 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