NEW THERAPEUTIC OPPORTUNITIES IN ALZHEIMER'S DISEASE: THE ROLE OF ANTI-AMYLOID ANTIBODIES: A COMPREHENSIVE REVIEW

Kacper Jaskulski; Katarzyna Kowalenko; Jan Szadkowski; Krzysztof Wichman; Hanna Kasprzak; Yana Lavrenchuk; Natalia Drobińska; Natalia Maria Leśniak; Julia Aleksandra Leśniak; Zuzanna Olszowiec

doi:10.31435/ijitss.3(51).2026.6427

Authors

Kacper Jaskulski Central Clinical Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0006-1631-8058
Katarzyna Kowalenko M. Sklodowska-Curie Provincial Hospital in Zgierz, Parzeczewska 35, 95-100 Zgierz, Poland https://orcid.org/0009-0003-5582-9713
Jan Szadkowski M. Sklodowska-Curie Provincial Hospital in Zgierz, Parzeczewska 35, 95-100 Zgierz, Poland https://orcid.org/0009-0009-4276-8636
Krzysztof Wichman M. Sklodowska-Curie Provincial Hospital in Zgierz, Parzeczewska 35, 95-100 Zgierz, Poland https://orcid.org/0009-0006-8073-6211
Hanna Kasprzak Norbert Barlicki Memorial Teaching Hospital No. 1 of the Medical University of Lodz, ul. dr. Stefana Kopcińskiego 22, 90-153 Łódź, Poland https://orcid.org/0009-0000-9038-1035
Yana Lavrenchuk Norbert Barlicki Memorial Teaching Hospital No. 1 of the Medical University of Lodz, ul. dr. Stefana Kopcińskiego 22, 90-153 Łódź, Poland https://orcid.org/0009-0001-1510-2902
Natalia Drobińska M. Sklodowska-Curie Provincial Hospital in Zgierz, Parzeczewska 35, 95-100 Zgierz, Poland https://orcid.org/0009-0006-9295-7564
Natalia Maria Leśniak Central Clinical Hospital of the Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0006-0815-6554
Julia Aleksandra Leśniak Central Clinical Hospital of the Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0005-7375-5951
Zuzanna Olszowiec M. Sklodowska-Curie Provincial Hospital in Zgierz, Parzeczewska 35, 95-100 Zgierz, Poland https://orcid.org/0009-0003-6775-8086

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6427

Keywords:

Beta-Amyloid, Alzheimer’s Disease, Aducanumab, Lecanemab, Donanemab, Monoclonal Antibodies, Aducanumab, Amyloid Target Therapy

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuronal loss, and the accumulation of β-amyloid plaques and tau pathology. For many years, pharmacological treatment has been limited to symptomatic therapies, including acetylcholinesterase inhibitors and memantine, which provide only modest clinical benefits without modifying disease progression. The development of anti-amyloid monoclonal antibodies has introduced the first disease-modifying therapeutic approach targeting the underlying pathology of AD. Agents such as aducanumab, lecanemab, and donanemab reduce cerebral amyloid burden through selective targeting of different forms of β-amyloid. Clinical trials, including CLARITY AD and TRAILBLAZER-ALZ 2, have demonstrated that these therapies can slow cognitive decline in patients with early-stage AD, although their efficacy depends on disease stage and patient selection. Despite remaining challenges, including safety concerns and the risk of amyloid-related imaging abnormalities, anti-amyloid therapies represent a major advancement in the treatment of Alzheimer’s disease and mark a transition toward disease-modifying strategies.

References

Sheppard, O., & Coleman, M. (2020). Alzheimer’s disease: Etiology, neuropathology and pathogenesis. In X. Huang (Ed.), Alzheimer’s disease: Drug discovery (pp. 1–22). Exon Publications. https://doi.org/10.36255/exonpublications.alzheimersdisease.2020.ch1

Cummings, J. L., Vinters, H. V., Cole, G. M., & Khachaturian, Z. S. (1998). Alzheimer’s disease: Etiologies, pathophysiology, cognitive reserve, and treatment opportunities. Neurology, 51(1 Suppl. 1), S2–S17. https://doi.org/10.1212/WNL.51.1_SUPPL_1.S2

Armstrong, R. A. (2011). The pathogenesis of Alzheimer’s disease: A reevaluation of the “amyloid cascade hypothesis.” International Journal of Alzheimer’s Disease, 2011, 630865. https://doi.org/10.4061/2011/630865

Reitz, C. (2012). Alzheimer’s disease and the amyloid cascade hypothesis: A critical review. International Journal of Alzheimer’s Disease, 2012, 369808. https://doi.org/10.1155/2012/369808

Lane, C. A., Hardy, J., & Schott, J. M. (2018). Alzheimer’s disease. European Journal of Neurology, 25(1), 59–70. https://doi.org/10.1111/ene.13439

Dou, K.-X., Tan, M.-S., Tan, C.-C., Cao, X.-P., Hou, X.-H., Guo, Q.-H., Tan, L., Mok, V., & Yu, J.-T. (2018). Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer’s disease: A network meta-analysis of 41 randomized controlled trials. Alzheimer’s Research & Therapy, 10, 126. https://doi.org/10.1186/s13195-018-0457-9

Muayqil, T., & Camicioli, R. (2012). Systematic review and meta-analysis of combination therapy with cholinesterase inhibitors and memantine in Alzheimer’s disease and other dementias. Dementia and Geriatric Cognitive Disorders Extra, 2(1), 546–572. https://doi.org/10.1159/000343479

Matsunaga, S., Kishi, T., & Iwata, N. (2015). Combination therapy with cholinesterase inhibitors and memantine for Alzheimer’s disease: A systematic review and meta-analysis. International Journal of Neuropsychopharmacology, 18(5), pyu115. https://doi.org/10.1093/ijnp/pyu115

Reitz, C., Brayne, C., & Mayeux, R. (2011). Epidemiology of Alzheimer disease. Nature Reviews Neurology, 7(3), 137–152. https://doi.org/10.1038/nrneurol.2011.2

Dou, K.-X., Tan, M.-S., Tan, C.-C., Cao, X.-P., Hou, X.-H., Guo, Q.-H., Tan, L., Mok, V., & Yu, J.-T. (2018). Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer’s disease: A network meta-analysis of 41 randomized controlled trials. Alzheimer’s Research & Therapy, 10, 126. https://doi.org/10.1186/s13195-018-0457-9

Leng, F., & Edison, P. (2021). Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nature Reviews Neurology, 17, 157–172. https://doi.org/10.1038/s41582-020-00435-y

Khartabil, N., & Awaness, A. (2025). Targeting amyloid pathology in early Alzheimer’s: The promise of donanemab-azbt. Pharmacy, 13(1), 23. https://doi.org/10.3390/pharmacy13010023

McDade, E., Cummings, J. L., Dhadda, S., Swanson, C. J., Reyderman, L., Kanekiyo, M., Koyama, A., Irizarry, M., Kramer, L. D., & Bateman, R. J. (2022). Lecanemab in patients with early Alzheimer’s disease: Detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimer’s Research & Therapy, 14(1), 191. https://doi.org/10.1186/s13195-022-01124-2

Noguchi-Shinohara, M., Shuta, K., Murakami, H., Mori, Y., Komatsu, J., Kobayashi, C., Hersch, S., Horie, K., & Ono, K. (2025). Lecanemab-associated amyloid-β protofibril in cerebrospinal fluid correlates with biomarkers of neurodegeneration in Alzheimer’s disease. Annals of Neurology, 97(5), 993–1006. https://doi.org/10.1002/ana.27175

Leuzy, A., Bollack, A., Pellegrino, D., Teunissen, C. E., La Joie, R., Rabinovici, G. D., Franzmeier, N., Johnson, K., Barkhof, F., Shaw, L. M., Arkhipenko, A., Schindler, S. E., Honig, L. S., Moscoso Rial, A., Schöll, M., Zetterberg, H., Blennow, K., Hansson, O., & Farrar, G. (2025). Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer’s disease. Alzheimer’s & Dementia, 21(3), e14528. https://doi.org/10.1002/alz.14528

Liao, W., Yu, Q., Chen, B., Chen, H., Zou, L., Xie, H., Chen, H., Wang, C., Li, Y., Gao, X., Guo, H., Yang, Y., She, Z., Zeng, Q., Zhang, Z., Li, G., Feng, S., Lin, H., Ouyang, J., . . . Liu, J. (2026). Effectiveness, safety, and biomarker dynamics of lecanemab in Chinese Alzheimer’s disease population: A multicenter real-world study. Alzheimer’s & Dementia, 22(3), e71231. https://doi.org/10.1002/alz.71231

Rahman, A., Hossen, M. A., Chowdhury, M. F. I., Bari, S., Tamanna, N., Sultana, S. S., Haque, S. N., Al Masud, A., & Saif-Ur-Rahman, K. M. (2023). Aducanumab for the treatment of Alzheimer’s disease: A systematic review. Psychogeriatrics, 23(3), 512–522. https://doi.org/10.1111/psyg.12944

Medel Sánchez, A., Ortiz Hernández, A., Moreno Moreno, R. A., Salas López, D., & colleagues. (2024). Aducanumab in Alzheimer’s disease: A comparative study of its effects on dementia and mild cognitive impairment. Cureus, 16(12), e75907. https://doi.org/10.7759/cureus.75907

Torres, A., Camargo, L., & López, N. (2024). Aducanumab: Una mirada dos años después de su aprobación. Biomédica, 44(Suppl. 1), 42–46. https://doi.org/10.7705/biomedica.6967

van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., Froelich, L., Katayama, S., Sabbagh, M., Vellas, B., Watson, D., Dhadda, S., Irizarry, M., Kramer, L. D., & Iwatsubo, T. (2023). Lecanemab in early Alzheimer’s disease. The New England Journal of Medicine, 388(1), 9–21. https://doi.org/10.1056/NEJMoa2212948

Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., Collins, E. C., Solomon, P., Salloway, S., & Mintun, M. A. (2023). Donanemab in early symptomatic Alzheimer disease: The TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA, 330(6), 512–527. https://doi.org/10.1001/jama.2023.13239

Mintun, M. A., Lo, A. C., Evans, C. D., Wessels, A. M., Ardayfio, P. A., Andersen, S. W., Shcherbinin, S., Sparks, J., Sims, J. R., Brys, M., Apostolova, L. G., Salloway, S. P., & Skovronsky, D. M. (2021). Donanemab in early Alzheimer’s disease. The New England Journal of Medicine, 384(18), 1691–1704. https://doi.org/10.1056/NEJMoa2100708

Menegaz de Almeida, A., Leite, M., Lopes, L. M., Lima, P. G., Barros, M. L. S., Pinheiro, S. R., Andrade, Í., Viana, P., Morbach, V., Marinheiro, G., de Oliveira, R., & Pinheiro, A. C. (2024). Gantenerumab for early Alzheimer’s disease: A systematic review and meta-analysis. Expert Review of Neurotherapeutics, 24(9), 929–936. https://doi.org/10.1080/14737175.2024.2367016

Sperling, R. A., Donohue, M. C., Raman, R., Rafii, M. S., Johnson, K., Masters, C. L., van Dyck, C. H., Iwatsubo, T., Marshall, G. A., Yaari, R., Mancini, M., Holdridge, K. C., Case, M., Sims, J. R., & Aisen, P. S. (2023). Trial of solanezumab in preclinical Alzheimer’s disease. The New England Journal of Medicine, 389(12), 1096–1107. https://doi.org/10.1056/NEJMoa2305032

Sato, K., & Iwatsubo, T. (2024). Anti-amyloid antibody drugs as disease-modifying therapies for Alzheimer’s disease. Brain and Nerve, 76(9), 991–995. https://doi.org/10.11477/mf.1416202723

van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., Froelich, L., Katayama, S., Sabbagh, M., Vellas, B., Watson, D., Dhadda, S., Irizarry, M., Kramer, L. D., & Iwatsubo, T. (2023). Lecanemab in early Alzheimer’s disease. The New England Journal of Medicine, 388(1), 9–21. https://doi.org/10.1056/NEJMoa2212948

Karran, E., & De Strooper, B. (2022). The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics. Nature Reviews Drug Discovery, 21(4), 306–318. https://doi.org/10.1038/s41573-022-00391-w

Ebell, M. H., Barry, H. C., Baduni, K., & Grasso, G. (2024). Clinically important benefits and harms of monoclonal antibodies targeting amyloid for the treatment of Alzheimer disease: A systematic review and meta-analysis. The Annals of Family Medicine, 22(1), 50–62. https://doi.org/10.1370/afm.3050

Cogswell, P. M., Andrews, T. J., Barakos, J. A., Barkhof, F., Bash, S., Benayoun, M. D., Chiang, G. C., Franceschi, A. M., Jack, C. R., Jr., Pillai, J. J., Poussaint, T. Y., Raji, C. A., Ramanan, V. K., Tanabe, J., Tanenbaum, L., Whitlow, C. T., Yu, F. F., Zaharchuk, G., Zeinah, M., & Benzinger, T. S. (2025). Alzheimer disease anti-amyloid immunotherapies: Imaging recommendations and practice considerations for monitoring of amyloid-related imaging abnormalities. AJNR American Journal of Neuroradiology, 46(1), 24–32. https://doi.org/10.3174/ajnr.A8469

Cummings, J., Apostolova, L., Rabinovici, G. D., Atri, A., Aisen, P., Greenberg, S., Hendrix, S., Selkoe, D., Weiner, M., Petersen, R. C., & Salloway, S. (2023). Lecanemab: Appropriate use recommendations. The Journal of Prevention of Alzheimer’s Disease, 10(3), 362–377. https://doi.org/10.14283/jpad.2023.30

Levien, T. L., & Baker, D. E. (2024). Lecanemab. Hospital Pharmacy, 59(5), 519–528. https://doi.org/10.1177/00185787231185869

Villain, N., Planche, V., & Levy, R. (2022). High-clearance anti-amyloid immunotherapies in Alzheimer’s disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects. Revue Neurologique, 178(10), 1011–1030. https://doi.org/10.1016/j.neurol.2022.06.012

Karran, E., & De Strooper, B. (2022). The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics. Nature Reviews Drug Discovery, 21(4), 306–318. https://doi.org/10.1038/s41573-022-00391-w

Avgerinos, K. I., Manolopoulos, A., Ferrucci, L., & Kapogiannis, D. (2024). Critical assessment of anti-amyloid-β monoclonal antibodies effects in Alzheimer’s disease: A systematic review and meta-analysis highlighting target engagement and clinical meaningfulness. Scientific Reports, 14(1), 25741. https://doi.org/10.1038/s41598-024-75204-8