{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:17:08Z","timestamp":1791328628089,"version":"4.3.1"},"reference-count":18,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5500","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2000,12,22]]},"abstract":"<jats:p>Plasma A\u03b242 (amyloid \u03b242 peptide) is invariably elevated in early-onset familial Alzheimer's disease (AD), and it is also increased in the first-degree relatives of patients with typical late-onset AD (LOAD). To detect LOAD loci that increase A\u03b242, we used plasma A\u03b242 as a surrogate trait and performed linkage analysis on extended AD pedigrees identified through a LOAD patient with extremely high plasma A\u03b2. Here, we report linkage to chromosome 10 with a maximal lod score of 3.93 at 81 centimorgans close to D10S1225. Remarkably, linkage to the same region was obtained independently in a genome-wide screen of LOAD sibling pairs. These results provide strong evidence for a novel LOAD locus on chromosome 10 that acts to increase A\u03b2.<\/jats:p>","DOI":"10.1126\/science.290.5500.2303","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:47:44Z","timestamp":1027763264000},"page":"2303-2304","source":"Crossref","is-referenced-by-count":293,"title":["Linkage of Plasma A\u03b242 to a Quantitative Locus on Chromosome 10 in Late-Onset Alzheimer's Disease Pedigrees"],"prefix":"10.1126","volume":"290","author":[{"given":"Nilufer","family":"Ertekin-Taner","sequence":"first","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neill","family":"Graff-Radford","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda H.","family":"Younkin","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Eckman","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Baker","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Adamson","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Ronald","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Blangero","sequence":"additional","affiliation":[{"name":"Southwest Foundation for Biomedical Research, San Antonio, TX 78245, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hutton","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Younkin","sequence":"additional","affiliation":[{"name":"Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/360672a0"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8424174"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8191290"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80230-5"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-864"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/383710a0"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","unstructured":"S. G. Younkin Neurobiol. Aging 21 (1S) S136 (abstract 612) (2000).","DOI":"10.1016\/S0197-4580(00)82409-4"},{"key":"e_1_3_1_9_2","unstructured":"Web tables are available at www.sciencemag.org\/cgi\/content\/full\/290\/5500\/2303\/DC1."},{"key":"e_1_3_1_10_2","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1086\/301844","volume":"62","author":"Almasy L.","year":"1998","unstructured":"Almasy L., Blangero J., Am. J. Hum. Genet. 62, 1198 (1998).","journal-title":"Am. J. Hum. Genet."},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7939663"},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/ng0397-273","volume":"15","author":"Comuzzie A. G.","year":"1997","unstructured":"Comuzzie A. G., et al., Nature Genet. 15, 273 (1997).","journal-title":"Nature Genet."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.2337\/diab.45.5.687","volume":"45","author":"Clement K.","year":"1996","unstructured":"Clement K., et al., Diabetes 45, 687 (1996).","journal-title":"Diabetes"},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/hmg\/8.2.237","volume":"8","author":"Kehoe P.","year":"1999","unstructured":"Kehoe P., et al., Hum. Mol. Genet. 8, 237 (1999).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1002\/1098-2272(2000)19:1+<::AID-GEPI2>3.0.CO;2-Y","volume":"19","author":"Blangero J.","year":"2000","unstructured":"Blangero J., Williams J. T., Almasy L., Genet. Epidemiol. 19S1, S8 (2000).","journal-title":"Genet. Epidemiol."},{"key":"e_1_3_1_16_2","unstructured":"IDE is an interesting candidate because there are several reports linking A\u03b2 degradation with IDE activity but this gene is 30 cM distal to the peak identified by our linkage analysis. We have moreover found no potential pathogenic variants by sequencing 90% of the IDE coding region in 11 members from our collection of pedigrees."},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5500.2302"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5500.2304"},{"key":"e_1_3_1_19_2","unstructured":"We thank C. E. Billings E. E. Croston L. A. Crump R. M. Fletcher E. C. Jobli R. L. Lawson L. M. Makarov J. G. Pagdanganan and F. C. Parfitt for the family collections; F. T. Pishotta T. Dyer and C. Peterson for expert technical assistance with computing; and the LOAD families for their support and participation. Supported by a grant from Clarice and Robert Smith Alzheimer Disease Research Center grant P50 AG16574 National Institute on Aging grant AG06656 and NIH grant MH59490 (J.B.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.290.5500.2303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:55:39Z","timestamp":1705139739000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.290.5500.2303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12,22]]},"references-count":18,"journal-issue":{"issue":"5500","published-print":{"date-parts":[[2000,12,22]]}},"alternative-id":["10.1126\/science.290.5500.2303"],"URL":"https:\/\/doi.org\/10.1126\/science.290.5500.2303","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12,22]]}}}