Aducanumab and Lecanemab: Target Specificity, Mechanisms and Clinical Outcomes in Alzheimer’s Disease

Authors

  • Shutong Zhang

DOI:

https://doi.org/10.61173/yhcven77

Keywords:

Monoclonal antibody, Aducanumab, Lecanemab, amyloid-beta accumulation, Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is one of the major unmet medical needs as a neurodegenerative disease associated with cognitive impairment and amyloid-beta (Aβ) accumulation. Unfortunately, current drug development for AD is based on treatment with only symptomatic therapies; there is no available drug able to influence the disease process. Anti-Aβ monoclonal antibodies have been shown as the promising strategy for AD therapy. However, little is known about the dissimilarities of these drugs in terms of target, mechanisms, and clinical effects. This review discusses the differences between two anti-Aβ antibodies – aducanumab and lecanemab, including target selectivity, mechanisms of action, structure, and clinical effectiveness. In particular, this review demonstrates that aducanumab interacts with the insoluble form of the protein, causing serious side effects, whereas lecanemab selectively binds the dangerous soluble protofibrillar form of Aβ. The importance of the state of Aβ aggregation for AD treatment has been revealed through the analysis of the drugs.

References

[1] Liu E, Zhang Y, Wang J Z. Updates in Alzheimer's disease: from basic research to diagnosis and therapies. Translational Neurodegeneration, 2024, 13(1): 45.

[2] Buccellato F R, D’Anca M, Tartaglia G M, et al. Treatment of Alzheimer’s disease: beyond symptomatic therapies. International Journal of Molecular Sciences, 2023, 24(18): 13900.

[3] Sehar U, Rawat P, Reddy A P, et al. Amyloid beta in aging and Alzheimer’s disease. International Journal of Molecular Sciences, 2022, 23(21): 12924.

[4] Li J, Liao W, Huang D, et al. Current strategies of detecting Aβ species and inhibiting Aβ aggregation: Status and prospects. Coordination Chemistry Reviews, 2023, 495: 215375.

[5] Söderberg L, Johannesson M, Nygren P, et al. Lecanemab, aducanumab, and gantenerumab—binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for Alzheimer's disease. Neurotherapeutics, 2023, 20(1): 195-206.

[6] Xiong M, Dahlén A, Roshanbin S, et al. Antibody engagement with amyloid‐beta does not inhibit [11C] PiB binding for PET imaging. Journal of Neurochemistry, 2024, 168(9): 2601-2610.

[7] Ameen T B, Kashif S N, Abbas S M I, et al. Unraveling Alzheimer’s: the promise of aducanumab, lecanemab, and donanemab. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery, 2024, 60(1): 72.

[8] Cascella R, Bigi A, Cremades N, et al. Effects of oligomer toxicity, fibril toxicity and fibril spreading in synucleinopathies. Dean&Francis ISSN 2959-409X Cellular and Molecular Life Sciences, 2022, 79(3): 174.

[9] Kaplan J M, Gibbs E, Coutts J A, et al. Relationship between efficacy and preferential targeting of soluble Aβ aggregates. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 2025, 11(4): e70184.

[10] Salloway S, Chalkias S, Barkhof F, et al. Amyloidrelated imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurology, 2022, 79(1): 13-21.

[11] Arndt J W, Qian F, Smith B A, et al. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. Scientific Reports, 2018, 8(1): 6412.

[12] Albertini G, Zielonka M, Cuypers M L, et al. The Alzheimer’s therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia. Nature Neuroscience, 2026, 29(1): 100-110.

[13] Ford C T. Predicting the molecular interactions of lecanemab, the new FDA-approved monoclonal antibody for Alzheimer’s disease. Colby Ford Blog, 2023.

[14] Tampi R R, Forester B P, Agronin M. Aducanumab: evidence from clinical trial data and controversies. Drugs in Context, 2021, 10: 1-12.

[15] Budd Haeberlein S, Aisen P S, Barkhof F, et al. Two randomized phase 3 studies of aducanumab in early Alzheimer’s disease. Journal of Prevention of Alzheimer's Disease, 2022, 9(2): 197-210.

[16] Berry D A, Dhadda S, Kanekiyo M, et al. Lecanemab for patients with early Alzheimer disease: Bayesian analysis of a phase 2b dose-finding randomized clinical trial. JAMA Network Open, 2023, 6(4): e237230.

[17] Qiao Y, Chi Y, Zhang Q, et al. Safety and efficacy of lecanemab for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. Frontiers in Aging Neuroscience, 2023, 15: 1169499.

Downloads

Published

2026-08-13