{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:47:26Z","timestamp":1792396046975,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014505","name":"R. Howard Webster Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009408","name":"Fondation Brain Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Amyloid beta (A\u03b2)\u2010directed antibodies have shown varying degrees of efficacy against Alzheimer's disease (AD). This study explored the relationship between targeting of A\u03b2 molecular species and therapeutic efficacy\/adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Surface plasmon resonance was used to measure binding of various A\u03b2\u2010directed antibodies to monomers and soluble oligomers from AD brains. Plaque reactivity was assessed by immunohistochemistry and immunofluorescence. Antibody PMN310 was tested in AD mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Pan\u2010A\u03b2 reactive antibodies that failed in the clinic lost the ability to bind AD brain oligomers when competing with monomers. Lecanemab, aducanumab, and donanemab, which slowed cognitive decline, and early stage PMN310 and ACU193 showed a greater ability to withstand monomer competition. All antibodies bound plaque except for PMN310. In mouse models, PMN310 protected cognition and was not associated with microhemorrhages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results suggest that selectivity for soluble toxic oligomers correlates with clinical efficacy, potentially attenuating monomer competition and amyloid\u2010related imaging abnormalities (ARIA).<\/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>Selectivity for toxic A\u03b2 oligomers has potential to maximize efficacy and safety.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Avoidance of A\u03b2 monomers increases binding to toxic AD brain oligomers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Avoidance of A\u03b2 plaque\/vascular deposits reduces the risk of ARIA.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70184","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T17:06:22Z","timestamp":1764349582000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Relationship between efficacy and preferential targeting of soluble A\u03b2 aggregates"],"prefix":"10.1002","volume":"11","author":[{"given":"Johanne M.","family":"Kaplan","sequence":"first","affiliation":[{"name":"ProMIS Neurosciences One Broadway  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebrima","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane A.","family":"Coutts","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhao","sequence":"additional","affiliation":[{"name":"ProMIS Neurosciences One Broadway  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S.","family":"Plotkin","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy and Genome Sciences and Technology Program University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Cashman","sequence":"additional","affiliation":[{"name":"ProMIS Neurosciences One Broadway  Cambridge Massachusetts USA"},{"name":"Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2022.30"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.09.023"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1372"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-179941"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1782"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200119"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041413"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31825fdf18"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46306-5"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt272"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126355"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2214981"},{"key":"e_1_2_8_16_1","doi-asserted-by":"crossref","unstructured":"LannfeltL S\u00f6derberg L. 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