EFFECTIVENESS OF LECANEMAB AND DONANEMAB TREATMENT FOR EARLY ALZHEIMER’S DISEASE
Abstract
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, tau neurofibrillary tangles, and other pathological factors like neuroinflammation and oxidative stress. This review discusses the effectiveness of Lanacemab and Donanemab - new anti-amyloid monoclonal antibodies- for the treatment of early Alzheimer’s Disease. While no cure exists, current symptomatic treatments are complemented by emerging disease-modifying therapies (DMTs). Recent breakthroughs with anti-amyloid monoclonal antibodies, Lecanemab and Donanemab, show promise in slowing disease progression. Clinical trials like CLARITY-AD for Lecanemab and TRAILBLAZER-ALZ 2 for Donanemab demonstrated significant reductions in brain amyloid and a slowed cognitive and functional decline in early AD. Lecanemab selectively targets Aβ protofibrils, while Donanemab targets N-terminally truncated Aβ in plaques, both facilitating amyloid clearance. These DMTs, though associated with side effects like ARIA, mark a pivotal shift towards targeting underlying AD pathology, offering hope for more effective interventions and potentially preventive strategies, such as those explored in the TRAILBLAZER-ALZ 3 trial.
References
Kumar A, Tsao JW, Sidhu J, Goyal A. Alzheimer Disease. National Library of Medicine. Published February 12, 2024. https://www.ncbi.nlm.nih.gov/books/NBK499922/
Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules. 2020;25(24):5789. doi:https://doi.org/10.3390/molecules25245789
Marzia Perluigi, Fabio Di Domenico, D. Allan Butterfield. Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease. Physiological Reviews. 2024;104(1):103-197. doi:https://doi.org/10.1152/physrev.00030.2022
Bhuvanasai Vejandla, Savani S, Rohith Appalaneni, Veeravalli RS, Sai Sravya Gude. Alzheimer’s Disease: The Past, Present, and Future of a Globally Progressive Disease. Cureus. Published online January 5, 2024. doi:https://doi.org/10.7759/cureus.51705
Dubois B, von Arnim C, Burnie N, Bozeat S, Cummings JL. Biomarkers in Alzheimer’s disease: role in early and differential diagnosis and recognition of atypical variants. Alzheimer’s Research & Therapy. 2023;15(1). doi:https://doi.org/10.1186/s13195-023-01314-6
Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s & dementia. 2024;20(8). doi:https://doi.org/10.1002/alz.13859
R. Monteiro Ana, Barbosa Daniel José, Fernando R, Renata S. Alzheimer’s disease: Insights and New Prospects in Disease pathophysiology, Biomarkers and disease-modifying Drugs. Biochemical Pharmacology. 2023;211(0006-2952):115522-115522. doi:https://doi.org/10.1016/j.bcp.2023.115522
Twarowski B, Herbet M. Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review. International Journal of Molecular Sciences. 2023;24(7):6518. doi:https://doi.org/10.3390/ijms24076518
Tuppo EE, Arias HR. The role of inflammation in Alzheimer’s disease. The international journal of biochemistry & cell biology. 2005;37(2):289-305. doi:https://doi.org/10.1016/j.biocel.2004.07.009
Lane CA, Hardy J, Schott JM. Alzheimer’s disease. European Journal of Neurology. 2017;25(1):59-70. doi:https://doi.org/10.1111/ene.13439
Guan PP, Cao LL, Wang P. Elevating the Levels of Calcium Ions Exacerbate Alzheimer’s Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau. International Journal of Molecular Sciences. 2021;22(11):5900. doi:https://doi.org/10.3390/ijms22115900
Chen Z, Zhong C. Oxidative stress in Alzheimer’s disease. Neuroscience Bulletin. 2014;30(2):271-281. doi:https://doi.org/10.1007/s12264-013-1423-y
H. Ferreira-Vieira T, M. Guimaraes I, R. Silva F, M. Ribeiro F. Alzheimer’s disease: Targeting the Cholinergic System. Current Neuropharmacology. 2016;14(1):101-115. doi:https://doi.org/10.2174/1570159x13666150716165726
Rossi AS, Galla L, Chiara Gomiero, et al. Calcium Signaling and Mitochondrial Function in Presenilin 2 Knock-Out Mice: Looking for Any Loss-of-Function Phenotype Related to Alzheimer’s Disease. Cells. 2021;10(2):204-204. doi:https://doi.org/10.3390/cells10020204
Maria Victoria Fernandez, Liu M, Aleksandra Beric, et al. Genetic and multi-omic resources for Alzheimer disease and related dementia from the Knight Alzheimer Disease Research Center. Scientific Data. 2024;11(1). doi:https://doi.org/10.1038/s41597-024-03485-9
Oatman SR, Reddy JS, Quicksall Z, et al. Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer’s disease related proteins. Molecular Neurodegeneration. 2023;18(1). doi:https://doi.org/10.1186/s13024-022-00592-2
Stefaniak O, Dobrzyńska M, Drzymała-Czyż S, Przysławski J. Diet in the Prevention of Alzheimer’s Disease: Current Knowledge and Future Research Requirements. Nutrients. 2022;14(21):4564. doi:https://doi.org/10.3390/nu14214564
Qiu C, Kivipelto M, Von Strauss E. Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention. Alzheimer’s Disease and Mild Cognitive Impairment. 2009;11(2):111-128. doi:https://doi.org/10.31887/dcns.2009.11.2/cqiu
Jack CR, Andrews JS, Beach TG, et al. Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s & dementia. 2024;20(8). doi:https://doi.org/10.1002/alz.13859
Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia. 2011;7(3):280-292. doi:https://doi.org/10.1016/j.jalz.2011.03.003
Lyketsos CG, Carrillo MC, Ryan JM, et al. Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimer’s & Dementia. 2011;7(5):532-539. doi:https://doi.org/10.1016/j.jalz.2011.05.2410
Cummings JL, Tong G, Ballard C. Treatment Combinations for Alzheimer’s Disease: Current and Future Pharmacotherapy Options. Journal of Alzheimer’s Disease. 2019;67(3):779-794. doi:https://doi.org/10.3233/jad-180766
Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG, Jonas DE. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis. Clinical Interventions in Aging. 2008;3(2):211. Accessed August 9, 2025. https://pmc.ncbi.nlm.nih.gov/articles/pmid/18686744/
Birks JS, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database of Systematic Reviews. 2018;2(6). doi:https://doi.org/10.1002/14651858.cd001190.pub3
Annicchiarico R, Federici A, Pettenati C, Caltagirone C. Rivastigmine in Alzheimer’s disease: Cognitive function and quality of life. Therapeutics and Clinical Risk Management. 2007;3(6):1113. Accessed August 9, 2025. https://pmc.ncbi.nlm.nih.gov/articles/pmid/18516265/
Müller T. Rivastigmine in the treatment of patients with Alzheimer’s disease. Neuropsychiatric Disease and Treatment. 2007;3(2):211-218. doi:https://doi.org/10.2147/nedt.2007.3.2.211
Khoury R, Rajamanickam J, Grossberg GT. An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine. Therapeutic Advances in Drug Safety. 2018;9(3):171-178. doi:https://doi.org/10.1177/2042098617750555
Birks JS, Chong LY, Grimley Evans J. Rivastigmine for Alzheimer’s disease. Cochrane Database of Systematic Reviews. 2015;9(9). doi:https://doi.org/10.1002/14651858.cd001191.pub4
Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of Acetylcholinesterase Inhibitors in Alzheimer’s Disease. Neuropharmacology. 2020;190(1):108352. doi:https://doi.org/10.1016/j.neuropharm.2020.108352
Wattmo C, Jedenius E, Blennow K, Wallin ÅK. Dose and plasma concentration of galantamine in Alzheimer’s disease - clinical application. Alzheimer’s Research & Therapy. 2013;5(1):2. doi:https://doi.org/10.1186/alzrt156
Folch J, Busquets O, Ettcheto M, et al. Memantine for the Treatment of Dementia: A Review on its Current and Future Applications. Perry G, Avila J, Tabaton M, Zhu X, eds. Journal of Alzheimer’s Disease. 2018;62(3):1223-1240. doi:https://doi.org/10.3233/jad-170672
Khoury R, Grysman N, Gold J, Patel K, Grossberg GT. The role of 5 HT6-receptor antagonists in Alzheimer’s disease: an update. Expert Opinion on Investigational Drugs. 2018;27(6):523-533. doi:https://doi.org/10.1080/13543784.2018.1483334
Tucker S, Möller C, Tegerstedt K, et al. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. Journal of Alzheimer’s disease : JAD. 2015;43(2):575-588. doi:https://doi.org/10.3233/JAD-140741
Magnusson K, Sehlin D, Syvänen S, et al. Specific uptake of an amyloid-β protofibril-binding antibody-tracer in AβPP transgenic mouse brain. Journal of Alzheimer’s disease: JAD. 2013;37(1):29-40. doi:https://doi.org/10.3233/JAD-130029
Sehlin D, Englund H, Simu B, et al. Large Aggregates Are the Major Soluble Aβ Species in AD Brain Fractionated with Density Gradient Ultracentrifugation. Bush AI, ed. PLoS ONE. 2012;7(2):e32014. doi:https://doi.org/10.1371/journal.pone.0032014
C N, A WD, Cb E, et al. The “Arctic” APP Mutation (E693G) Causes Alzheimer’s Disease by Enhanced Abeta Protofibril Formation. Nature neuroscience. Published September 1, 2001. https://pubmed.ncbi.nlm.nih.gov/11528419/
Sims JR, Zimmer JA, Evans CD, et al. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA. 2023;330(6). doi:https://doi.org/10.1001/jama.2023.13239
Rabinovici GD, Selkoe DJ, Schindler SE, et al. Donanemab: Appropriate use recommendations. The Journal of Prevention of Alzheimer’s Disease. Published online March 27, 2025:100150. doi:https://doi.org/10.1016/j.tjpad.2025.100150
Nandhini Jayaprakash, Karthikeyan Elumalai. Translational Medicine in Alzheimer’s Disease: The Journey of Donanemab From Discovery to Clinical Application. Chronic Diseases and Translational Medicine. Published online December 16, 2024. doi:https://doi.org/10.1002/cdt3.155
Jin M, Noble JM. What’s in It for Me? Contextualizing the Potential Clinical Impacts of Lecanemab, Donanemab, and Other Anti-β-amyloid Monoclonal Antibodies in Early Alzheimer’s Disease. eneuro. 2024;11(9):ENEURO.0088-24.2024. doi:https://doi.org/10.1523/eneuro.0088-24.2024
Shcherbinin S, Evans CD, Lu M, et al. Association of Amyloid Reduction After Donanemab Treatment With Tau Pathology and Clinical Outcomes. JAMA Neurology. 2022;79(10):1015. doi:https://doi.org/10.1001/jamaneurol.2022.2793
Wessels AM, Rentz DM, Case M, Lauzon S, Sims JR. Integrated Alzheimer’s Disease Rating Scale: Clinically meaningful change estimates. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2022;8(1). doi:https://doi.org/10.1002/trc2.12312
Niidome T, Ishikawa Y, Ogawa T, Nakagawa M, Nakamura Y. [Mechanism of action and clinical trial results of Lecanemab (Leqembi® 200 mg, 500 mg for Intravenous Infusion), a novel treatment for Alzheimer’s disease]. Nihon Yakurigaku Zasshi Folia Pharmacologica Japonica. 2024;159(3):173-181. doi:https://doi.org/10.1254/fpj.24005
van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine. 2022;388(1):9-21. doi:https://doi.org/10.1056/nejmoa2212948
Chen C, Katayama S, Lee JH, et al. Clarity AD: Asian regional analysis of a phase III trial of lecanemab in early Alzheimer’s disease. The Journal of Prevention of Alzheimer s Disease. Published online April 1, 2025:100160-100160. doi:https://doi.org/10.1016/j.tjpad.2025.100160
H van DC, Randall B, Sharon C, et al. Lecanemab clarity AD: results from a randomised, double-blind phase 3 early Alzheimer’s disease trial. Journal of Neurology, Neurosurgery & Psychiatry. 2023;94(Suppl 1):A45-A46. doi:https://doi.org/10.1136/JNNP-2023-ABN.139
Cohen S, van Dyck CH, Gee M, et al. Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease. The Journal of Prevention of Alzheimer’s Disease. 2023;10(4):771-777. doi:https://doi.org/10.14283/jpad.2023.123
Costa T, Enrico Premi, Liloia D, Franco Cauda, Jordi Manuello. Unleashing the Power of Bayesian Re-Analysis: Enhancing Insights into Lecanemab (Clarity AD) Phase III Trial Through Informed t-Test. Journal of Alzheimer’s Disease. 2023;95(3):1059-1065. doi:https://doi.org/10.3233/jad-230589
Villain N, Planche V, Lilamand M, et al. Lecanemab for early Alzheimer’s disease: Appropriate use recommendations from the French federation of memory clinics. The journal of prevention of Alzheimer’s disease. 2025;12(4):100094. doi:https://doi.org/10.1016/j.tjpad.2025.100094
Honig LS, Sabbagh MN, Christopher, et al. Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimer’s research & therapy. 2024;16(1). doi:https://doi.org/10.1186/s13195-024-01441-8
Cummings J, Apostolova L, Rabinovici GD, et al. Lecanemab: Appropriate Use Recommendations. The Journal of Prevention of Alzheimer’s Disease. 2023;10(3). doi:https://doi.org/10.14283/jpad.2023.30
Vitek GE, Decourt B, Sabbagh MN. Lecanemab (BAN2401): an anti–beta-amyloid monoclonal antibody for the treatment of Alzheimer disease. Expert Opinion on Investigational Drugs. 2023;32(2). doi:https://doi.org/10.1080/13543784.2023.2178414
Satlin A, Wang J, Logovinsky V, et al. Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2016;2(1):1-12. doi:https://doi.org/10.1016/j.trci.2016.01.001
Swanson CJ, Zhang Y, Dhadda S, et al. A randomized, double-blind, Phase 2b proof-of-concept Clinical Trial in Early Alzheimer’s Disease with lecanemab, an anti-Aβ Protofibril Antibody. Alzheimer’s Research & Therapy. 2021;13(1). doi:https://doi.org/10.1186/s13195-021-00813-8
Sperling RA, Jack CR, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: Recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimer’s & Dementia. 2011;7(4):367-385. doi:https://doi.org/10.1016/j.jalz.2011.05.2351
Khartabil N, Awaness A. Targeting Amyloid Pathology in Early Alzheimer’s: The Promise of Donanemab-Azbt. Pharmacy. 2025;13(1):23. doi:https://doi.org/10.3390/pharmacy13010023
Loeffler DA. Antibody-Mediated Clearance of Brain Amyloid-β: Mechanisms of Action, Effects of Natural and Monoclonal Anti-Aβ Antibodies, and Downstream Effects. Journal of Alzheimer’s disease reports. 2023;7(1):873-899. doi:https://doi.org/10.3233/adr-230025
Sato S, Hatakeyama N, Fujikoshi S, Katayama S, Katagiri H, Sims JR. Donanemab in Japanese Patients with Early Alzheimer’s Disease: Subpopulation Analysis of the TRAILBLAZER-ALZ 2 Randomized Trial. Neurology and Therapy. Published online April 6, 2024. doi:https://doi.org/10.1007/s40120-024-00604-x
Høilund-Carlsen PF, Alavi A, Barrio JR, et al. Donanemab, another anti-Alzheimer’s drug with risk and uncertain benefit. Ageing research reviews. 2024;99:102348. doi:https://doi.org/10.1016/j.arr.2024.102348
Zimmer JA, Ardayfio P, Wang H, et al. Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease. JAMA Neurology. Published online March 10, 2025. doi:https://doi.org/10.1001/jamaneurol.2025.0065
Pontecorvo MJ, Lu M, Burnham SC, et al. Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease. JAMA Neurology. 2022;79(12). doi:https://doi.org/10.1001/jamaneurol.2022.3392
Wessels AM, Dennehy EB, Dowsett SA, Dickson SP, Hendrix SB. Meaningful Clinical Changes in Alzheimer Disease Measured With the iADRS and Illustrated Using the Donanemab TRAILBLAZER-ALZ Study Findings. Neurology: Clinical Practice. 2023;13(2). doi:https://doi.org/10.1212/CPJ.0000000000200127
Views:
35
Downloads:
28
Copyright (c) 2025 Maria Ufniarska, Tomasz Ufniarski, Aleksandra Piech, Karolina Pasierb, Karol Poplicha, Martyna Grodzińska, Bartłomiej Siuzdak, Justyna Moszkowicz, Piotr Sobkiewicz, Patrycja Kardasz, Marta Jutrzenka, Patrycja Ucieklak
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
