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In June 2021, <jats:italic>Aduhelm<\/jats:italic> (Aducanumab) became the first U.S. Food and Drug Administration (FDA) approved treatment for AD based on the amyloid hypothesis in which sparked controversy. This meta-analysis aims to investigate the efficacy of amyloid-beta targeting interventions at all stages of the disease including the prodromal or mild cognitive impairment (MCI) stage compared to placebo. All completed and terminated Phase III trials are assessed to provide a comprehensive overview of interventions targeting amyloid-beta to inform the legitimacy of the amyloid hypothesis.<\/jats:p>","DOI":"10.1371\/journal.pone.0307761","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T17:23:42Z","timestamp":1727457822000},"page":"e0307761","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Do beta-amyloid-targeted interventions improve cognition, physical functioning, and overt behaviour of Alzheimer\u2019s Disease (AD) patients: Protocol for meta-analysis of Phase 3 clinical trials both completed and terminated"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4877-205X","authenticated-orcid":true,"given":"Chelsea Ann","family":"Stellick (Bedrejo)","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-900X","authenticated-orcid":true,"given":"Andrew","family":"Greenshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Paulden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-3715","authenticated-orcid":true,"given":"Sidney","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-3639","authenticated-orcid":true,"given":"R. 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