{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T06:04:55Z","timestamp":1791612295167,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,6,27]],"date-time":"2013-06-27T00:00:00Z","timestamp":1372291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL-111062"],"award-info":[{"award-number":["HL-111062"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL-91867"],"award-info":[{"award-number":["HL-91867"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mayo Alzheimer's Disease Research Center"},{"name":"AHA","award":["0835436N"],"award-info":[{"award-number":["0835436N"]}]},{"name":"AHA","award":["12POST8550003"],"award-info":[{"award-number":["12POST8550003"]}]},{"name":"Clinical Pharmacology Training Grant","award":["T32 GM08685"],"award-info":[{"award-number":["T32 GM08685"]}]},{"name":"Samuel Johnson Foundation for Genomics of Addiction Program at Mayo Clinic"},{"DOI":"10.13039\/100007048","name":"Mayo Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007048","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Aging and the presence of cerebrovascular disease are associated with increased incidence of Alzheimer's disease. A common feature of aging and cerebrovascular disease is decreased endothelial nitric oxide (NO). We studied the effect of a loss of endothelium derived NO on amyloid precursor protein (APP) related phenotype in late middle aged (LMA) (14\u201315\u00a0month) endothelial nitric oxide synthase deficient (\n                    <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice. APP, \u03b2\u2010site APP cleaving enzyme (BACE) 1, and amyloid beta (A\u03b2) levels were significantly higher in the brains of LMA\n                    <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice as compared with LMA wild\u2010type controls. APP and A\u03b2\n                    <jats:sub>1\u201040<\/jats:sub>\n                    were increased in hippocampal tissue of\n                    <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice as compared with wild\u2010type mice. LMA\n                    <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice displayed an increased inflammatory phenotype as compared with LMA wild\u2010type mice. Importantly, LMA\n                    <jats:styled-content style=\"fixed-case\">eNOS<\/jats:styled-content>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice performed worse in a radial arm maze test of spatial learning and memory as compared with LMA wild\u2010type mice. These data suggest that chronic loss of endothelial NO may be an important contributor to both A\u03b2 related pathology and cognitive decline.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12334-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>\n                  <jats:p>Cardiovascular risk factors are associated with increased incidence of Alzheimer's disease (AD). A common feature of these risk factors is decreased endothelial nitric oxide (NO). We observed, in mice deficient in endothelial nitric oxide synthase, increased amyloid precursor protein (APP), \u03b2\u2010site APP cleaving enzyme 1, amyloid beta levels, microglial activation, and impaired spatial memory. This suggests chronic loss of endothelial NO may be an important contributor to the pathogenesis of sporadic AD.<\/jats:p>","DOI":"10.1111\/jnc.12334","type":"journal-article","created":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T08:01:55Z","timestamp":1370678515000},"page":"691-700","source":"Crossref","is-referenced-by-count":148,"title":["Endothelial nitric oxide deficiency promotes Alzheimer's disease pathology"],"prefix":"10.1111","volume":"127","author":[{"given":"Susan A.","family":"Austin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anantha V.","family":"Santhanam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Hinton","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doo\u2010Sup","family":"Choi","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvonimir S.","family":"Katusic","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Mayo Clinic Rochester Minnesota USA"},{"name":"Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4586-11.2012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-4257(97)87907-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.233080"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3233\/JAD-2012-121351","article-title":"Supplementation of nitric oxide attenuates AbetaPP and BACE1 protein in cerebral microcirculation of eNOS\u2010deficient mice","volume":"33","author":"Austin S. 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