{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:25:55Z","timestamp":1786976755563,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2023,12]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n \n Apolipoprotein E (\n APOE<\/jats:italic>\n ) \u03b54 may interact with response to amyloid\u2010targeting therapies.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Aggregate data from trials enrolling participants with amyloid\u2010positive, early symptomatic Alzheimer's disease (AD) were analyzed for disease progression.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Pooled analysis of potentially efficacious antibodies lecanemab, aducanumab, solanezumab, and donanemab shows slightly better efficacy in\n APOE<\/jats:italic>\n \u03b54 carriers than in non\u2010carriers. Carrier and non\u2010carrier mean (95% confidence interval) differences from placebo using Clinical Dementia Rating Scale\u2013Sum of Boxes (CDR\u2010SB) were \u20130.30 (\u20130.478, \u20130.106) and \u20130.20 (\u20130.435, 0.042) and AD Assessment Scale\u2013Cognitive subscale (ADAS\u2010Cog) values were \u20131.01 (\u20131.577, \u20130.456) and \u20130.80 (\u20131.627, 0.018), respectively. Decline in the\n APOE<\/jats:italic>\n \u03b54 non\u2010carrier placebo group was equal to or greater than that in carriers across multiple scales. Probability of study success increases as the representation of the carrier population increases.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n We hypothesize that\n APOE<\/jats:italic>\n \u03b54 carriers have same or better response than non\u2010carriers to amyloid\u2010targeting therapies and similar or less disease progression with placebo in amyloid\u2010positive trials.\n <\/jats:p>\n <\/jats:sec>\n \n HIGHLIGHTS<\/jats:title>\n \n \n \n \n Amyloid\u2010targeting therapies had slightly greater efficacy in apolipoprotein E (\n APOE<\/jats:italic>\n ) \u03b54 carriers.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Clinical decline is the same\/slightly faster in amyloid\u2010positive\n APOE<\/jats:italic>\n \u03b54 non\u2010carriers.\n <\/jats:p>\n <\/jats:list-item>\n \n Prevalence of non\u2010carriers in trial populations could impact outcomes.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.13128","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:20:31Z","timestamp":1684491631000},"page":"5407-5417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["APOE<\/i>\n \u03b54's impact on response to amyloid therapies in early symptomatic Alzheimer's disease: Analyses from multiple clinical trials"],"prefix":"10.1002","volume":"19","author":[{"given":"Cynthia D.","family":"Evans","sequence":"first","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JonDavid","family":"Sparks","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Hauck","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Mintun","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"},{"name":"Avid Radiopharmaceuticals a wholly owned subsidiary of Eli Lilly and Company Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Sims","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.5847"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002923"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2016.03.012"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00884-7"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0594-74"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2620"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00391-w"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4669"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-210685"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","unstructured":"SuzukiK HirakawaA IharaR et\u00a0al.Alzheimer's Disease Neuroimaging Initiative Japanese Alzheimer's Disease Neuroimaging Initiative. 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