{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:07:04Z","timestamp":1784038024459,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,11]]},"group-title":"Neuroscience","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"crossref","award":["ALZDISCOVERY-1049110"],"award-info":[{"award-number":["ALZDISCOVERY-1049110"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AG064016"],"award-info":[{"award-number":["R01AG064016"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"John L. 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Therefore, we assessed the interaction between\n                  <jats:italic>APOE<\/jats:italic>\n                  genotype and age across a comprehensive set of cerebrovascular and related outcomes. We performed\n                  <jats:italic>in vivo<\/jats:italic>\n                  imaging,\n                  <jats:italic>ex vivo<\/jats:italic>\n                  cerebral artery studies, behavioral tests, and molecular analyses in male and female homozygous\n                  <jats:italic>APOE3<\/jats:italic>\n                  and\n                  <jats:italic>APOE4<\/jats:italic>\n                  mice at \u223c6 months (young) and \u223c24 months (old).\n                  <jats:italic>APOE4<\/jats:italic>\n                  interacted with old age to lead to deficits in brain volume and greater microglia content. Old\n                  <jats:italic>APOE4<\/jats:italic>\n                  mice also exhibited greater cerebral artery vasoconstriction to endothelin-1 (ET-1) than old\n                  <jats:italic>APOE3<\/jats:italic>\n                  mice, a response concomitant with age-and genotype-related differences in the expression of ET-1 receptors and endothelin-converting enzyme. While we found several interactions between age and\n                  <jats:italic>APOE<\/jats:italic>\n                  genotype, only age impacted cognitive function, cerebral artery endothelial function, and arterial stiffness. In summary, we found that brain volume, neuroinflammation, and ET-1-related outcomes were influenced by the interaction of\n                  <jats:italic>APOE<\/jats:italic>\n                  genotype and age, while other outcomes were affected only by age. As such, an altered ET-1 response and greater neuroinflammation may contribute to the increased risk for LOAD in\n                  <jats:italic>APOE4<\/jats:italic>\n                  carriers.\n                <\/jats:p>","DOI":"10.64898\/2026.07.07.736860","type":"posted-content","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T21:05:10Z","timestamp":1783803910000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>APOE4<\/i>\n                  genotype and old age interact to impact cerebrovascular function, brain volume, and neuroinflammation in mice"],"prefix":"10.64898","author":[{"given":"Mackenzie N","family":"Kehmeier","sequence":"first","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young D","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail E","family":"Cullen","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Helfgott Research Institute, National University of Natural Medicine, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Leonhardt","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddie","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tucker","family":"Cleveland","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naly","family":"Setthavongsack","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine, School of Medicine, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall L.","family":"Woltjer","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine, School of Medicine, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M.","family":"Pike","sequence":"additional","affiliation":[{"name":"Advanced Imaging Research Center, Department of Biomedical Engineering, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil J","family":"Alkayed","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-4545","authenticated-orcid":false,"given":"Ashley E","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, University of Oregon, Eugene, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071406250936000_2026.07.07.736860v1.1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3233\/JAD-2010-1221","article-title":"Alzheimer\u2019s Disease and the \u03b2-Amyloid Peptide","volume":"19","year":"2010","journal-title":"J Alzheimers 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