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This could be due to their sub-optimal design and\/or deployment; alternatively, their limited efficiency could be intrinsic. Distinguishing between the two is of great importance considering the acute need of efficient AD therapy and tremendous resources being invested in its pursuit. The present study analyzes the mode of operation of lecanemab and donanemab within the framework of recently proposed Amyloid Cascade Hypothesis 2.0 and concludes that the second possibility is correct. It suggests that substantial improvement of the efficiency of these drugs in symptomatic AD is unlikely and proposes the alternative therapeutic strategy.<\/jats:p>","DOI":"10.3233\/jad-230164","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T12:22:48Z","timestamp":1684498968000},"page":"1277-1284","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":46,"title":["Effect of Lecanemab and Donanemab in Early Alzheimer\u2019s Disease: Mechanistic Interpretation in the Amyloid Cascade Hypothesis 2.0 Perspective"],"prefix":"10.1177","volume":"93","author":[{"given":"Vladimir","family":"Volloch","sequence":"first","affiliation":[{"name":"Harvard School of Dental Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Rits-Volloch","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital","place":["USA"]},{"name":"Harvard Medical School","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-022-03081-0"},{"key":"e_1_3_5_4_2","unstructured":"GallagherJ (2023) Alzheimer\u2019s-slowing drug labelled historic. https:\/\/www.bbc.com\/news\/health-63060019."},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/ADR-220031"},{"key":"e_1_3_5_7_2","first-page":"523","article-title":"Oligomer-specific amyloid-beta toxicity in cell models is mediated by selective uptake","volume":"9","author":"Chafekar S","year":"2008","unstructured":"ChafekarS, BaasF, ScheperW (2008) Oligomer-specific amyloid-beta toxicity in cell models is mediated by selective uptake. 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