{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:00:53Z","timestamp":1791939653995,"version":"4.3.4"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,3]]},"abstract":"<jats:p>Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +\/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +\/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.<\/jats:p>","DOI":"10.1073\/pnas.90.5.1977","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:40:05Z","timestamp":1149064805000},"page":"1977-1981","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3267,"title":["Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease."],"prefix":"10.1073","volume":"90","author":[{"given":"W J","family":"Strittmatter","sequence":"first","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M","family":"Saunders","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Schmechel","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Pericak-Vance","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Enghild","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G S","family":"Salvesen","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A D","family":"Roses","sequence":"additional","affiliation":[{"name":"Department of Medicine (Neurology), Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,3]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.5.1977","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:33:27Z","timestamp":1649856807000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.5.1977"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,3]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1993,3]]}},"alternative-id":["10.1073\/pnas.90.5.1977"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.5.1977","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,3]]},"assertion":[{"value":"1993-03-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}