{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:22:26Z","timestamp":1790144546571,"version":"4.0.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T00:00:00Z","timestamp":1520467200000},"content-version":"vor","delay-in-days":66,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1RFAG041705\u201001A1"],"award-info":[{"award-number":["1RFAG041705\u201001A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008483","name":"NOMIS Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001109","name":"Flinn Foundation","doi-asserted-by":"publisher","award":["1862"],"award-info":[{"award-number":["1862"]}],"id":[{"id":"10.13039\/100001109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013327","name":"H. Lundbeck A\/S","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013327","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003037","name":"Elan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003037","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006775","name":"GE Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007306","name":"Arizona Department of Health Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010718","name":"Foundation for Biomedical Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008483","name":"NOMIS Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001109","name":"Flinn Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001109","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Autosomal\u2010dominant Alzheimer's disease (ADAD) represents a crucial population for identifying prevention strategies that might modify disease course for cognitively unimpaired individuals at high imminent risk for developing symptoms due to Alzheimer's disease (AD), that\u00a0is, who have \u201cpreclinical\u201d AD. Crenezumab is an antiamyloid monoclonal antibody that binds monomeric and aggregated forms of amyloid \u03b2, with highest affinity for oligomers; it is in development for early stages of sporadic AD and for ADAD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a prospective, randomized, double\u2010blind, placebo\u2010controlled phase 2 study of the efficacy of crenezumab versus placebo in asymptomatic <jats:italic>PSEN1<\/jats:italic> E280A mutation carriers from family kindreds with ADAD in Colombia. Participants were randomized to receive either crenezumab or placebo for 260\u00a0weeks. The study was designed to enroll a planned total of 300 participants, including 200 preclinical mutation carriers (approximately 100 treatment, 100 placebo) and an additional control group of mutation noncarriers from the same family kindreds included to mask mutation carrier status (100 placebo only). The primary outcome is change in the Alzheimer's Prevention Initiative ADAD Composite Cognitive Test Score from baseline to week 260. Secondary outcomes include time to progression to mild cognitive impairment due to AD or dementia due to AD; changes in dementia severity, memory, and overall neurocognitive functioning; and changes in amyloid\u2013positron emission tomography, fluorodeoxyglucose\u2013positron emission tomography, magnetic resonance imaging volumes, and cerebrospinal fluid levels of \u03b2 amyloid, tau, and p\u2010tau. Safety and tolerability are assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two hundred fifty\u2010two participants were enrolled between December 2013 and February\u00a02017.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We describe the first large\u2010scale, potentially label\u2010enabling clinical trial of a preclinical treatment for ADAD. Results from this trial will inform on the efficacy of crenezumab for delaying onset of, slowing decline in, or preventing cognitive impairment in individuals with preclinical ADAD and will foster an improved understanding of AD biomarkers and their relationship to clinical outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.trci.2018.02.002","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T09:54:57Z","timestamp":1520502897000},"page":"150-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["The Alzheimer's Prevention Initiative Autosomal\u2010Dominant Alzheimer's Disease Trial: A study of crenezumab versus placebo in preclinical <i>PSEN1<\/i> E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal\u2010dominant Alzheimer's disease, including a placebo\u2010treated noncarrier cohort"],"prefix":"10.1002","volume":"4","author":[{"given":"Pierre N.","family":"Tariot","sequence":"first","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Lopera","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Langbaum","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego School of Medicine La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Hendrix","sequence":"additional","affiliation":[{"name":"Pentara Corporation Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lon S.","family":"Schneider","sequence":"additional","affiliation":[{"name":"USC State of California Alzheimer's Disease Research and Clinical Center, Keck Medicine of USC Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rios\u2010Romenets","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Giraldo","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Acosta","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Tobon","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ramos","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Espinosa","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias Universidad de Antioquia, SIU Medell\u00edn Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Cho","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ward","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Clayton","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Friesenhahn","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard","family":"Mackey","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Honigberg","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sanabria Bohorquez","sequence":"additional","affiliation":[{"name":"Genentech, a Member of the Roche Group South San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Chen","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trisha","family":"Walsh","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Langlois","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Reiman","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Prevention Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1989.03430180093036"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21915"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606210"},{"key":"e_1_2_7_5_1","unstructured":"Alzheimer Disease & Frontotemporal Dementia Mutation Database. Available at:www.molgen.ua.ac.be\/admutations\/. Accessed March 16 2018."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001130"},{"key":"e_1_2_7_7_1","first-page":"35","article-title":"Autosomal\u2010dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease","volume":"2","author":"Bateman R.J.","year":"2011","journal-title":"Alzheimers Res. Ther"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000318238","article-title":"List of drugs in development for neurodegenerative diseases: update June 2010","volume":"8","author":"Kramp V.P.","year":"2011","journal-title":"Neurodegener Dis"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2008.02.016"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.88.9.1337"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.003"},{"key":"e_1_2_7_13_1","first-page":"55","article-title":"Descripcion de una familia con demencia presenil tipo Alzheimer","volume":"12","author":"Cornejo W.","year":"1987","journal-title":"Acta Med Colombiana"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1997)10:3<186::AID-HUMU2>3.0.CO;2-H"},{"key":"e_1_2_7_15_1","first-page":"173","article-title":"Demencia tipo Alzheimer con agregacion familiar en Antioquia, Colombia","volume":"10","author":"Lopera F.","year":"1994","journal-title":"Acta Neurol Colomb"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540340027028"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(10)70323-9"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/13803390601174151"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70227-2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2010.00469.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.617"},{"key":"e_1_2_7_22_1","first-page":"S232","article-title":"Reduced regional gray matter in cognitively normal young adults at genetic risk for early\u2010onset Alzheimer's disease","volume":"7","author":"Fleisher A.","year":"2011","journal-title":"Alzheimers Dement"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.253"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.1729"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39374"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4742-11.2012"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2351"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0695-06.2006"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.04.450"},{"key":"e_1_2_7_30_1","first-page":"214","article-title":"Amyloid PET imaging results from a study to evaluate the impact of crenezumab on fibrillar amyloid in patients with mild\u2010to\u2010moderate Alzheimer's disease.","volume":"1","author":"Salloway S.","year":"2014","journal-title":"J Prev Alz"},{"key":"e_1_2_7_31_1","first-page":"214","article-title":"Analysis of amyloid\u2010\u03b2 PET changes from the crenezumab anti\u2010A\u03b2 phase 2 trial using a pre\u2010specified cerebral white matter reference region\u2010of\u2010interest.","volume":"1","author":"Reiman E.M.","year":"2014","journal-title":"J Prev Alz"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e7586"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-158-3-201302050-00583"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.141.11.1356"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.39.9.1159"},{"issue":"2","key":"e_1_2_7_38_1","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1097\/00002093-199700112-00003","article-title":"Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer's Disease Assessment Scale that broaden its scope. The Alzheimer's Disease Cooperative Study","volume":"11","author":"Mohs R.C.","year":"1997","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1366728911000332"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_7_41_1","volume-title":"Raven Progressive Matrices","author":"Raven J.","year":"1976"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.11.2412-a"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1037\/h0093567"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1076\/jcen.20.3.310.823"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/87565648709540361"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.12.2308"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.5_Suppl_6.10S"},{"key":"e_1_2_7_48_1","first-page":"165","volume-title":"Clinical Gerontology: A Guide to Assessment and Intervention","author":"Sheikh J.I.","year":"1986"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610292001157"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13m08927"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2014.02.002"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1302513"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.177"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.04.001"}],"container-title":["Alzheimer's &amp; Dementia: Translational Research &amp; Clinical Interventions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352873718300052?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352873718300052?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.trci.2018.02.002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.trci.2018.02.002","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.trci.2018.02.002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T11:22:11Z","timestamp":1761477731000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.trci.2018.02.002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1016\/j.trci.2018.02.002"],"URL":"https:\/\/doi.org\/10.1016\/j.trci.2018.02.002","archive":["Portico"],"relation":{},"ISSN":["2352-8737","2352-8737"],"issn-type":[{"value":"2352-8737","type":"print"},{"value":"2352-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1]]},"assertion":[{"value":"2018-03-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}