{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:50:50Z","timestamp":1791395450918,"version":"4.3.3"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"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":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      While the apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54 allele promotes blood\u2013brain barrier (BBB) permeability and microstructural disruption, its specific contribution to white matter hyperintensity (WMH) pathological heterogeneity remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We measured BBB permeability (\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>trans<\/jats:sub>\n                      ) in 31 and microstructure in 59 cognitively normal older adults with WMHs and normal\u2010appearing white matter (NAWM) using dynamic contrast\u2010enhanced magnetic resonance imaging and restriction spectrum imaging (RSI). Linear mixed\u2010effects models (LMMs) examined differences between WMHs and NAWM by\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carriers,\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>trans<\/jats:sub>\n                      was elevated and restricted isotropic diffusion (RI) was reduced within WMHs compared to NAWM. This effect was absent in non\u2010carriers. In contrast, reduced restricted directional diffusion and elevated isotropic free water within WMHs was observed in both genotypes.\n                      <jats:italic>K<\/jats:italic>\n                      <jats:sub>trans<\/jats:sub>\n                      did not correlate with brain microstructure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our data suggest that WMHs comprise both\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\u2010related and\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54\u2010independent pathological components. These findings implicate neurovascular and non\u2010vascular mechanisms through which\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 may contribute to WMH pathological heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.70459","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:02:45Z","timestamp":1787205765000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>APOE<\/i>\n                    \u03b54\u2010related blood\u2013brain barrier disruption and\n                    <i>APOE<\/i>\n                    \u03b54\u2010independent microstructural abnormalities in white matter hyperintensities"],"prefix":"10.1002","volume":"18","author":[{"given":"Yuki","family":"Oi","sequence":"first","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seraphina K.","family":"Solders","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte S.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKenna E.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie T.","family":"Reas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California, San Diego  La Jolla California 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