{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:06:30Z","timestamp":1792508790223,"version":"4.5.0"},"reference-count":23,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5123","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1993,8,13]]},"abstract":"<jats:p>\n                    The apolipoprotein E type 4 allele (\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54) is genetically associated with the common late onset familial and sporadic forms of Alzheimer's disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 alleles in 42 families with late onset AD. Thus\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for\n                    <jats:italic>APOE<\/jats:italic>\n                    -\u03b54 was virtually sufficient to cause AD by age 80.\n                  <\/jats:p>","DOI":"10.1126\/science.8346443","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T19:05:09Z","timestamp":1160075109000},"page":"921-923","source":"Crossref","is-referenced-by-count":7703,"title":["Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families"],"prefix":"10.1126","volume":"261","author":[{"given":"E. H.","family":"Corder","sequence":"first","affiliation":[{"name":"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":"Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. J.","family":"Strittmatter","sequence":"additional","affiliation":[{"name":"Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. E.","family":"Schmechel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Neurology, and Neurobiology, Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710, and Durham VA Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. C.","family":"Gaskell","sequence":"additional","affiliation":[{"name":"Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. W.","family":"Small","sequence":"additional","affiliation":[{"name":"Neuropsychiatric Institute and Hospital, Center for Health Sciences, University of California, Los Angeles, CA 90024."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. D.","family":"Roses","sequence":"additional","affiliation":[{"name":"Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. L.","family":"Haines","sequence":"additional","affiliation":[{"name":"Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA 02129."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Pericak-Vance","sequence":"additional","affiliation":[{"name":"Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC 27710."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","unstructured":"SAS Institute Inc. SAS Technical Report P-217 SAS\/STAT Software: The PHREG Procedure Version 6 (1991)."},{"key":"e_1_2_1_2_1","unstructured":"SAS\/STAT User's Guide Release 6.03 Edition (1988)."},{"key":"e_1_2_1_3_1","unstructured":"SAS User's Guide: Statistics Version 5 Edition (1985)."},{"key":"e_1_2_1_4_1","unstructured":"CORDER E.H. unpublished data."},{"key":"e_1_2_1_5_1","unstructured":"Cox D. R. Analysis of Survival Data (1984)."},{"key":"e_1_2_1_6_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1172\/JCI109263","volume":"63","year":"1979","unstructured":"FARID, N.R., STUDY OF HUMAN LEUKOCYTE-D LOCUS RELATED ANTIGENS IN GRAVES-DISEASE, JOURNAL OF CLINICAL INVESTIGATION 63: 108 (1979).","journal-title":"JOURNAL OF CLINICAL INVESTIGATION"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_1_8_1","first-page":"135","volume":"52","year":"1993","unstructured":"GREENBERG, D.A., LINKAGE ANALYSIS OF NECESSARY DISEASE LOCI VERSUS SUSCEPTIBILITY LOCI, AMERICAN JOURNAL OF HUMAN GENETICS 52: 135 (1993).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_9_1","unstructured":"Koch G. G. Analysis of Categorical Data (1985)."},{"key":"e_1_2_1_10_1","first-page":"1178","volume":"2","year":"1984","unstructured":"LANGDON, N, GENETIC-MARKERS IN NARCOLEPSY, LANCET 2: 1178 (1984).","journal-title":"LANCET"},{"key":"e_1_2_1_11_1","unstructured":"Miller R. G. Survival Analysis (1981)."},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0006-8993(91)91092-F","volume":"541","year":"1991","unstructured":"NAMBA, Y, APOLIPOPROTEIN-E IMMUNOREACTIVITY IN CEREBRAL AMYLOID DEPOSITS AND NEUROFIBRILLARY TANGLES IN ALZHEIMERS-DISEASE AND KURU PLAQUE AMYLOID IN CREUTZFELDT-JAKOB DISEASE, BRAIN RESEARCH 541: 163 (1991).","journal-title":"BRAIN RESEARCH"},{"key":"e_1_2_1_13_1","first-page":"1034","volume":"48","year":"1991","unstructured":"PERICAKVANCE, M.A., LINKAGE STUDIES IN FAMILIAL ALZHEIMER-DISEASE - EVIDENCE FOR CHROMOSOME-19 LINKAGE, AMERICAN JOURNAL OF HUMAN GENETICS 48: 1034 (1991).","journal-title":"AMERICAN JOURNAL OF HUMAN GENETICS"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0014-4886(88)90220-8","volume":"102","year":"1988","unstructured":"PERICAKVANCE, M.A., GENETIC-LINKAGE STUDIES IN ALZHEIMERS-DISEASE FAMILIES, EXPERIMENTAL NEUROLOGY 102: 271 (1988).","journal-title":"EXPERIMENTAL NEUROLOGY"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1467"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411576"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.20.9649"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1292-330"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2880399"},{"key":"e_1_2_1_20_1","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1073\/pnas.90.5.1977","volume":"90","year":"1993","unstructured":"Strittmatter, W. J., Proc. Natl. Acad. Sci. U.S.A. 90: 1977 (1993).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1977"},{"key":"e_1_2_1_22_1","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1080\/01621459.1989.10478873","volume":"84","year":"1989","unstructured":"WEI, L.J., REGRESSION-ANALYSIS OF MULTIVARIATE INCOMPLETE FAILURE TIME DATA BY MODELING MARGINAL DISTRIBUTIONS, JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION 84: 1065 (1989).","journal-title":"JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION"},{"key":"e_1_2_1_23_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0304-3940(92)90444-C","volume":"135","year":"1992","unstructured":"WISNIEWSKI, T, APOLIPOPROTEIN-E - A PATHOLOGICAL CHAPERONE PROTEIN IN PATIENTS WITH CEREBRAL AND SYSTEMIC AMYLOID, NEUROSCIENCE LETTERS 135: 235 (1992).","journal-title":"NEUROSCIENCE LETTERS"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.8346443","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T06:14:09Z","timestamp":1705299249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.8346443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,8,13]]},"references-count":23,"journal-issue":{"issue":"5123","published-print":{"date-parts":[[1993,8,13]]}},"alternative-id":["10.1126\/science.8346443"],"URL":"https:\/\/doi.org\/10.1126\/science.8346443","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.723301123.793552982","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,8,13]]}}}