{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:33:05Z","timestamp":1787725985010,"version":"build-2784847793"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,25]],"date-time":"2023-12-25T00:00:00Z","timestamp":1703462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["1UF1AG046150"],"award-info":[{"award-number":["1UF1AG046150"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000957","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\/100015595","name":"GHR Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's Prevention Initiative Generation Study 1 evaluated amyloid beta (A\u03b2) active immunotherapy (vaccine) CAD106 and BACE\u20101 inhibitor umibecestat in cognitively unimpaired 60\u2010 to 75\u2010year\u2010old participants at genetic risk for Alzheimer's disease (AD). The study was reduced in size and terminated early. Results from the CAD106 cohort are presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Sixty\u2010five apolipoprotein E \u03b54 homozygotes with\/without amyloid deposition received intramuscular CAD106 450\u00a0\u03bcg (<jats:italic>n<\/jats:italic>\u00a0=\u00a042) or placebo (<jats:italic>n<\/jats:italic>\u00a0=\u00a023) at baseline; Weeks 1, 7, 13; and quarterly; 51 of them had follow\u2010up A\u03b2 positron emission tomography (PET) scans at 18 to 24 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>CAD106 induced measurable serum A\u03b2 immunoglobulin G titers in 41\/42 participants, slower rates of A\u03b2 plaque accumulation (mean [standard deviation] annualized change from baseline in amyloid PET Centiloid: \u22120.91[5.65] for CAD106 versus 8.36 [6.68] for placebo; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and three amyloid\u2010related imaging abnormality cases (one symptomatic).<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Despite early termination, these findings support the potential value of conducting larger prevention trials of A\u03b2 active immunotherapies in individuals at risk for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>This was the first amyloid\u2010lowering prevention trial in persons at genetic risk of late\u2010onset Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Active immunotherapy targeting amyloid (CAD106) was tested in this prevention trial.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CAD106 significantly slowed down amyloid plaque deposition in apolipoprotein E homozygotes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>CAD106 was generally safe and well tolerated, with only three amyloid\u2010related imaging abnormality cases (one symptomatic).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Such an approach deserves further evaluation in larger AD prevention trials.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13532","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T02:22:57Z","timestamp":1710555777000},"page":"1839-1850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Effects of the active amyloid beta immunotherapy CAD106 on PET measurements of amyloid plaque deposition in cognitively unimpaired <i>APOE<\/i> \u03b54 homozygotes"],"prefix":"10.1002","volume":"20","author":[{"given":"Marie\u2010Emmanuelle","family":"Riviere","sequence":"first","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Langbaum","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Scott","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Neurology Georgetown University Medical Center  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha O.","family":"Rinne","sequence":"additional","affiliation":[{"name":"Turku PET Centre University of Turku and Turku University Hospital  Turku Finland"},{"name":"Department of Neurology CRST \u2013 Clinical Research Services Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihan","family":"Sui","sequence":"additional","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Pharmaceuticals  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Cazorla","sequence":"additional","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Pharmaceuticals  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Ricart","sequence":"additional","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Farmaceutica SA  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Meneses","sequence":"additional","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Pharmaceuticals  East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Caputo","sequence":"additional","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre N.","family":"Tariot","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Reiman","sequence":"additional","affiliation":[{"name":"Banner Alzheimer's Institute  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Graf","sequence":"additional","affiliation":[{"name":"Clinical Development, Neuroscience Novartis Pharma AG  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt237"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2536"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.05.059"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70140-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0293-11.2011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2016.12.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.4668"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.02.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170072"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0339-y"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00014"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8346443"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002254"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14279-8"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809437"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341202"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.107"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2635903100"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500579102"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1076\/jcen.20.3.310.823"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01183-z"},{"key":"e_1_2_8_24_1","unstructured":"TariotP Marie\u2010Emmanuelle RiviereN Stephen S et\u00a0al Reversibility of mild worsening in cognition with umibecestat treatment : data from two randomized phase 2\/3 trials (Alzheimer's Prevention Initiative (API) Generation Study 1 and Study 2). In preparation.2023."},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00633-2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000073623.84147.A8"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-150448"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2023.27"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.04.001"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:52:12Z","timestamp":1759924332000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.13532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,25]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/alz.13532"],"URL":"https:\/\/doi.org\/10.1002\/alz.13532","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,25]]},"assertion":[{"value":"2023-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}