{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:31:22Z","timestamp":1792071082820,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","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":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>The monoclonal antibodies Aducanumab, Lecanemab, Gantenerumab, and Donanemab were developed for the treatment of Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We used single\u2010molecule detection and super\u2010resolution imaging to characterize the binding of these antibodies to diffusible amyloid beta (A\u03b2) aggregates generated\n                      <jats:italic>in<\/jats:italic>\n                      <jats:italic>\u2010<\/jats:italic>\n                      <jats:italic>vitro<\/jats:italic>\n                      and harvested from human brains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Lecanemab showed the best performance in terms of binding to the small\u2010diffusible A\u03b2 aggregates, affinity, aggregate coating, and the ability to bind to post\u2010translationally modified species, providing an explanation for its therapeutic success. We observed a Braak stage\u2013dependent increase in small\u2010diffusible aggregate quantity and size, which was detectable with Aducanumab and Gantenerumab, but not Lecanemab, showing that the diffusible A\u03b2 aggregates change with disease progression and the smaller aggregates to which Lecanemab preferably binds exist at higher quantities during earlier stages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings provide an explanation for the success of Lecanemab in clinical trials and suggests that Lecanemab will be more effective when used in early\u2010stage AD.<\/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>Anti amyloid beta therapeutics are compared by their diffusible aggregate binding characteristics.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In\u2010vitro and brain\u2010derived aggregates are tested using single\u2010molecule detection.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Lecanemab shows therapeutic success by binding to aggregates formed in early disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Lecanemab binds to these aggregates with high affinity and coats them better.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70086","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T02:43:57Z","timestamp":1746672237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Lecanemab preferentially binds to smaller aggregates present at early Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-5806","authenticated-orcid":false,"given":"Emre","family":"Fertan","sequence":"first","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff Y. L.","family":"Lam","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"},{"name":"Division of Life Science, The Hong Kong University of Science and Technology  Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Albertini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences VIB\u2010KU Leuven Center for Brain &amp; Disease Research  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Dewilde","sequence":"additional","affiliation":[{"name":"Laboraory for Therapeutic and Diagnostic Antibodies KU Leuven  Leuven Belgium"},{"name":"The KU Leuven Antibody Centre PharmABS  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhao","family":"Wu","sequence":"additional","affiliation":[{"name":"Yusuf Hamied Department of Chemistry University of Cambridge  Cambridge UK"},{"name":"UK Dementia Research Institute at University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwatomi E. 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