{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:49:22Z","timestamp":1777495762100,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,30]],"date-time":"2006-01-30T00:00:00Z","timestamp":1138579200000},"content-version":"vor","delay-in-days":2130,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2000,4]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Following the identification of the role of the apolipoprotein E (<jats:italic>APOE<\/jats:italic>) gene polymorphism in Alzheimer's disease (AD), this gene was examined in cerebral amyloid angiopathy (CAA). As in AD, the <jats:italic>APOE<\/jats:italic>\u025b4 allele was found to be associated with CAA. Lobar intracerebral hemorrhage is the major clinical manifestation of CAA. Initial studies on a small number of patients with CAA\u2010related hemorrhage (CAAH) identified overrepresentation of <jats:italic>APOE<\/jats:italic>\u025b4. However, it became clear that confounding bias from concomitant AD and the need for pathologically confirmed cases of CAAH would also have to be considered. A larger series of pathologically confirmed cases of CAAH, also assessed for AD pathology, found a surprising overrepresentation of the <jats:italic>APOE<\/jats:italic>\u025b2 allele. Because of the association between CAA and AD, it might have been predicted that patients with CAAH would have a low, rather than a high, \u025b2 frequency. The overrepresentation of <jats:italic>APOE<\/jats:italic>\u025b2 was present both in patients with and without AD, whereas a high \u025b4 frequency correlated with concomitant AD.<\/jats:p><jats:p>Further studies found that overrepresentation of <jats:italic>APOE<\/jats:italic>\u025b2 is specific for CAAH and is not found in intracranial hemorrhages due to other causes. In CAAH, <jats:italic>APOE<\/jats:italic>\u025b2 may interact with putative risk factors for hemorrhage, including antiplatelet\/anticoagulant medication, minor head trauma, and hypertension. Several microvascular abnormalities in amyloid\u2010laden blood vessels have been assumed to antedate CAAH and increase its likelihood. <jats:italic>APOE<\/jats:italic>\u025b2 has now been found to be associated with some of these vascular abnormalities, specifically a \u201cdouble\u2010barrel\u201d appearance and fibrinoid necrosis.<\/jats:p><jats:p>The currently favored interpretation is that <jats:italic>APOE<\/jats:italic>\u025b4 enhances deposition of amyloid\u2010\u03b2 protein in the walls of cerebral blood vessels, whereas \u025b2 is a risk factor for hemorrhage from amyloid\u2010laden blood vessels by promoting specific \u201cCAA\u2010associated vasculopathies.\u201d<\/jats:p>","DOI":"10.1111\/j.1749-6632.2000.tb06366.x","type":"journal-article","created":{"date-parts":[[2006,1,30]],"date-time":"2006-01-30T14:39:26Z","timestamp":1138631966000},"page":"176-179","source":"Crossref","is-referenced-by-count":82,"title":["Apolipoprotein E Genotype and Cerebral Amyloid Angiopathy\u2010related Hemorrhage"],"prefix":"10.1111","volume":"903","author":[{"given":"MARK O.","family":"McCARRON","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JAMES A.R.","family":"NICOLL","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,30]]},"reference":[{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1977"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91092-F"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300503"},{"key":"e_1_2_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9649"},{"key":"e_1_2_2_7_2","first-page":"2083","article-title":"Apolipoprotein E\u2010\u025b4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease","volume":"148","author":"Premkumar D.R.","year":"1996","journal-title":"Am. 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