{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:05:21Z","timestamp":1789038321225,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Alzheimer's disease (AD) is a neurological disorder with variability in pathology and clinical progression. AD patients may differ in individual\u2010level benefit from amyloid beta removal therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Random forest models were applied to the EMERGE trial to create an individual\u2010level treatment response (ITR) score which represents individual\u2010level benefit of high\u2010dose aducanumab relative to the placebo. This ITR score was used to test the existence of heterogeneity in treatment effect (HTE).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We found statistical evidence of HTE in the Clinical Dementia Rating\u2013Sum of Boxes (CDR\u2010SB;<jats:italic>P<\/jats:italic>\u00a0=\u00a0 0.034). The observed CDR\u2010SB benefit was 0.79 points greater in the group with the top 25% of ITR score compared to the remaining 75% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.020). Of note, the highest treatment responders had lower hippocampal volume, higher plasma phosphorylated tau 181 and a shorter duration of clinical AD at baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>This ITR analysis provides a proof of concept for precision medicine in future AD research and drug development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Emerging trials have shown a population\u2010level benefit from amyloid beta (A\u03b2) removal in slowing cognitive decline in early Alzheimer's disease (AD).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This work demonstrates significant heterogeneity of individual\u2010level treatment effect of aducanumab in early AD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The greatest clinical responders to A\u03b2 removal therapy have a pattern of more severe neurodegenerative process.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13431","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T07:04:22Z","timestamp":1698303862000},"page":"1102-1111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Precision medicine analysis of heterogeneity in individual\u2010level treatment response to amyloid beta removal in early Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Menglan","family":"Pang","sequence":"first","affiliation":[{"name":"Biogen Digital Health Biogen  Cambridge Massachusetts USA"},{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Gabelle","sequence":"additional","affiliation":[{"name":"Biogen Digital Health Biogen  Cambridge Massachusetts USA"},{"name":"Biogen  Cambridge Massachusetts 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