{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:40:45Z","timestamp":1790728845553,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Decades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta\u2010protein (A\u03b2). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease\u2010modifying A\u03b2 antibody for early AD. Secondary prevention trials with A\u03b2 antibodies are underway. We summarize peer\u2010reviewed evidence for targeting A\u03b2 and argue that regulators should consider approving new agents working by similar mechanisms (A\u03b2\u00a0antibodies and vaccines) based on robust amyloid lowering and reasonable safety. The urgent need to provide treatments to millions of mildly symptomatic patients suggests that AD should join other diseases for which standard approval is based on significant changes in mechanistically meaningful biomarkers coupled with safety. Robust amyloid lowering in secondary prevention trials of people who have amyloid plaques but are asymptomatic could also provide evidence of a change in the pathophysiological progression of AD as a basis for regulatory approval.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Thirteen key findings support amyloid beta as a cause of Alzheimer's disease (AD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Three immunotherapies lower amyloid and slow decline, allowing regulatory approval.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>New such agents could be considered for approval due to amyloid lowering and safety.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Urgency suggests AD may join diseases with approval due to a key biomarker + safety.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14342","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:35:05Z","timestamp":1731483305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The case for regulatory approval of amyloid\u2010lowering immunotherapies in Alzheimer's disease based on clearcut biomarker evidence"],"prefix":"10.1002","volume":"21","author":[{"given":"Paul","family":"Aisen","sequence":"first","affiliation":[{"name":"USC Alzheimer's Therapeutic Research Institute  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall J.","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Crowther","sequence":"additional","affiliation":[{"name":"TRIMTECH Therapeutics Ltd and Medical and More Ltd  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Cummings","sequence":"additional","affiliation":[{"name":"School of Integrated Health Sciences University of Nevada Las Vegas  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Global Alzheimer's Platform Foundation Washington  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Iwatsubo","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Kosco\u2010Vilbois","sequence":"additional","affiliation":[{"name":"AC Immune  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"McDade","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mohs","sequence":"additional","affiliation":[{"name":"Global Alzheimer's Platform Foundation Washington  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Scheltens","sequence":"additional","affiliation":[{"name":"Medical Center and EQT Life Sciences Amsterdam University  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reisa","family":"Sperling","sequence":"additional","affiliation":[{"name":"Dpartment of Neurology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Selkoe","sequence":"additional","affiliation":[{"name":"Dpartment of Neurology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010021\u201000269\u2010y"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000611\u20105"},{"key":"e_1_2_4_4_1","unstructured":"Alzheimer'sAlzheimeAssociation.2024 Alzheimer's Disease Facts and 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