{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T04:10:53Z","timestamp":1759032653078},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Background and Purpose<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Epidemiological findings and experimental data on transgenic mice show that Alzheimer\u2019s disease\u2013related changes render the brain more susceptible to ischemic damage. We studied whether the previously observed vulnerability in mice overexpressing the 751\u2013amino-acid isoform of human amyloid precursor protein (APP751) is regulated by human apolipoprotein E (apoE) alleles, which determine the relative risk for Alzheimer\u2019s disease and the susceptibility to various forms of acute brain damage.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Methods<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Aged apoE knock out (KO) mice, mice overexpressing APP751 in the apoE KO background and mice expressing either human apoE3 or apoE4 and APP751 in the apoE KO background were exposed to permanent occlusion of the middle cerebral artery (MCA). Infarct volumes were quantified from T\n            <jats:sub>2<\/jats:sub>\n            -weighted magnetic resonance images 24 hours after the MCA occlusion. Local cortical blood flow was monitored by laser Doppler flowmetry. Ischemia-induced microgliosis was detected by immunohistochemistry.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Results<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Overexpression of human APP751 significantly increased the infarct volumes in apoE KO mice. Furthermore, this APP751-induced ischemic vulnerability was attenuated by the coexpression of either human apoE isoform. MCA occlusion resulted in a similar relative reduction in cortical blood flow in all mouse groups. Vascular anatomy showed no variation in the MCA territory between the groups. Instead, the expression of human apoE isoforms reduced the ischemia-induced microgliosis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:bold>\n                  <jats:italic>Conclusions<\/jats:italic>\n                <\/jats:bold>\n                \u2014\n              <\/jats:italic>\n            <\/jats:bold>\n            Expression of either the human apoE3 or apoE4 isoform protects against the increased ischemic vulnerability observed in aged mice overexpressing human APP751, probably by modulating the inflammatory response induced by MCA occlusion.\n          <\/jats:p>","DOI":"10.1161\/01.str.0000020124.61998.bc","type":"journal-article","created":{"date-parts":[[2002,7,28]],"date-time":"2002-07-28T23:16:47Z","timestamp":1027898207000},"page":"1905-1910","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Expression of Human Apolipoprotein E Downregulates Amyloid Precursor Protein\u2013Induced Ischemic Susceptibility"],"prefix":"10.1161","volume":"33","author":[{"given":"Milla","family":"Koistinaho","sequence":"first","affiliation":[{"name":"From the A.I. Virtanen Institute for Molecular Sciences (M.K., M.I.K., R.A.K., J.K.), University of Kuopio, the Department of Clinical Pathology (J.K.), Kuopio University Hospital, and the National Bio-NMR Facility (M.I.K., R.A.K.), Kuopio, Finland; the Department of Neurology and Center for the Study of Nervous System Injury (D.M.H.), Washington University School of Medicine, St. Louis, Mo; and Scios Inc (L.S.H.), Sunnyvale, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikko I.","family":"Kettunen","sequence":"additional","affiliation":[{"name":"From the A.I. Virtanen Institute for Molecular Sciences (M.K., M.I.K., R.A.K., J.K.), University of Kuopio, the Department of Clinical Pathology (J.K.), Kuopio University Hospital, and the National Bio-NMR Facility (M.I.K., R.A.K.), Kuopio, Finland; the Department of Neurology and Center for the Study of Nervous System Injury (D.M.H.), Washington University School of Medicine, St. Louis, Mo; and Scios Inc (L.S.H.), Sunnyvale, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Holtzman","sequence":"additional","affiliation":[{"name":"From the A.I. Virtanen Institute for Molecular Sciences (M.K., M.I.K., R.A.K., J.K.), University of Kuopio, the Department of Clinical Pathology (J.K.), Kuopio University Hospital, and the National Bio-NMR Facility (M.I.K., R.A.K.), Kuopio, Finland; the Department of Neurology and Center for the Study of Nervous System Injury (D.M.H.), Washington University School of Medicine, St. Louis, Mo; and Scios Inc (L.S.H.), Sunnyvale, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risto A.","family":"Kauppinen","sequence":"additional","affiliation":[{"name":"From the A.I. Virtanen Institute for Molecular Sciences (M.K., M.I.K., R.A.K., J.K.), University of Kuopio, the Department of Clinical Pathology (J.K.), Kuopio University Hospital, and the National Bio-NMR Facility (M.I.K., R.A.K.), Kuopio, Finland; the Department of Neurology and Center for the Study of Nervous System Injury (D.M.H.), Washington University School of Medicine, St. Louis, Mo; and Scios Inc (L.S.H.), Sunnyvale, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda S.","family":"Higgins","sequence":"additional","affiliation":[{"name":"From the A.I. Virtanen Institute for Molecular Sciences (M.K., M.I.K., R.A.K., J.K.), University of Kuopio, the Department of Clinical Pathology (J.K.), Kuopio University Hospital, and the National Bio-NMR Facility (M.I.K., R.A.K.), Kuopio, Finland; the Department of Neurology and Center for the Study of Nervous System Injury (D.M.H.), Washington University School of Medicine, St. Louis, Mo; and Scios Inc (L.S.H.), Sunnyvale, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jari","family":"Koistinaho","sequence":"additional","affiliation":[{"name":"From the A.I. Virtanen Institute for Molecular Sciences (M.K., M.I.K., R.A.K., J.K.), University of Kuopio, the Department of Clinical Pathology (J.K.), Kuopio University Hospital, and the National Bio-NMR Facility (M.I.K., R.A.K.), Kuopio, Finland; the Department of Neurology and Center for the Study of Nervous System Injury (D.M.H.), Washington University School of Medicine, St. Louis, Mo; and Scios Inc (L.S.H.), Sunnyvale, Calif."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)01030-2"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.2.741"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261562998"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-05-01858.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3283935"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.19.030196.000413"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-02-00516.1997"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199805000-00001"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03550160069041"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-180"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/372092a0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-263"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6179"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.050004797"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04318-3"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91411-0"},{"key":"e_1_3_2_18_2","first-page":"818","volume":"227","year":"1997","unstructured":"Slooter AJ, Tang MX, van Duijn CM, Stern Y, Ott A, Bell K, Breteler MM, Van Broeckhoven C, Tatemichi TK, Tycko B, et al. 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