NEW DISEASE-MODIFYING THERAPIES IN ALZHEIMER’S DISEASE: A CLINICAL REVIEW OF LECANEMAB AND DONANEMAB
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.4885Keywords:
Lecanemab, Donanemab, Alzheimer’s Disease, ARIAAbstract
It has been widely suggested that monoclonal antibodies targeting amyloid-β represent a potentially disease-modifying therapeutic approach for Alzheimer’s disease (AD), offering an alternative to purely symptomatic treatments. In recent years, considerable research attention has focused on anti-amyloid strategies aimed at modifying the underlying pathophysiology of early symptomatic AD. Among the agents currently under investigation, lecanemab and donanemab have demonstrated consistent amyloid plaque reduction and statistically significant slowing of cognitive and functional decline in patients with mild cognitive impairment or mild dementia due to AD.
The present review aims to critically evaluate evidence from pivotal clinical trials of both therapies, with particular emphasis on efficacy outcomes, safety profiles, pharmacological characteristics, and regulatory approval status. Special attention is given to treatment-related risks, including amyloid-related imaging abnormalities (ARIA), as well as factors influencing patient eligibility, treatment initiation, and monitoring strategies in clinical practice.
Taken together, the available evidence suggests that amyloid-targeting monoclonal antibodies may provide a modest yet clinically meaningful benefit in carefully selected patients, while simultaneously highlighting ongoing challenges related to safety, implementation, and long-term therapeutic effectiveness.
References
2019 Alzheimer Europe yearbook: Estimating the prevalence of dementia in Europe. (2025, January 9). http://santesecu.public.lu/de/publications/a/alzheimer-yearbook-2019.html
2020 Alzheimer’s disease facts and figures. (2020). Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12068
2022 Alzheimer’s disease facts and figures. (2022). Alzheimer’s & Dementia, 18(4), 700–789. https://doi.org/10.1002/alz.12638
Alagaratnam, J., von Widekind, S., De Francesco, D., Underwood, J., Edison, P., Winston, A., Zetterberg, H., & Fidler, S. (2021). Correlation between CSF and blood neurofilament light chain protein: A systematic review and meta-analysis. BMJ Neurology Open, 3(1), e000143. https://doi.org/10.1136/bmjno-2021-000143
Alawode, D. O. T., Heslegrave, A. J., Fox, N. C., & Zetterberg, H. (2021). Donanemab removes Alzheimer’s plaques: What is special about its target? The Lancet Healthy Longevity, 2(7), e395–e396. https://doi.org/10.1016/S2666-7568(21)00144-6
Angioni, D., Middleton, L., Bateman, R., Aisen, P., Boxer, A., Sha, S., Zhou, J., Gerlach, I., Raman, R., Fillit, H., Salloway, S., Sperling, R., Vellas, B., & Cummings, J. (2025). Challenges and opportunities for novel combination therapies in Alzheimer’s disease: A report from the EU/US CTAD Task Force. The Journal of Prevention of Alzheimer’s Disease, 12(6), Article 100163. https://doi.org/10.1016/j.tjpad.2025.100163
Bateman, R. J., Aisen, P. S., De Strooper, B., Fox, N. C., Lemere, C. A., Ringman, J. M., Salloway, S., Sperling, R. A., Windisch, M., & Xiong, C. (2011). Autosomal-dominant Alzheimer’s disease: A review and proposal for the prevention of Alzheimer’s disease. Alzheimer’s Research & Therapy, 3(1), 1. https://doi.org/10.1186/alzrt59
Bayer, T. A. (2022). Pyroglutamate Aβ cascade as drug target in Alzheimer’s disease. Molecular Psychiatry, 27(4), 1880–1885. https://doi.org/10.1038/s41380-021-01409-2
Berry, D. A., Dhadda, S., Kanekiyo, M., Li, D., Swanson, C. J., Irizarry, M., Kramer, L. D., & Berry, S. M. (2023). Lecanemab for patients with early Alzheimer disease. JAMA Network Open, 6(4), e237230. https://doi.org/10.1001/jamanetworkopen.2023.7230
Bloom, G. S. (2014). Amyloid-β and tau: The trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurology, 71(4), 505–508. https://doi.org/10.1001/jamaneurol.2013.5847
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
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019). Alzheimer’s disease drug development pipeline: 2019. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 5, 272–293. https://doi.org/10.1016/j.trci.2019.05.008
DeMattos, R. B., Lu, J., Tang, Y., Racke, M. M., DeLong, C. A., Tzaferis, J. A., Hole, J. T., Forster, B. M., McDonnell, P. C., Liu, F., Kinley, R. D., Jordan, W. H., & Hutton, M. L. (2012). A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer’s disease mice. Neuron, 76(5), 908–920. https://doi.org/10.1016/j.neuron.2012.10.029
Di Benedetto, G., Burgaletto, C., Bellanca, C. M., Munafò, A., Bernardini, R., & Cantarella, G. (2022). Role of microglia and astrocytes in Alzheimer’s disease: From neuroinflammation to Ca2+ homeostasis dysregulation. Cells, 11(17), 2728. https://doi.org/10.3390/cells11172728
Dickson, S. P., Wessels, A. M., Dowsett, S. A., Mallinckrodt, C., Sparks, J. D., Chatterjee, S., & Hendrix, S. (2023). “Time saved” as a demonstration of clinical meaningfulness and illustrated using the donanemab TRAILBLAZER-ALZ study findings. The Journal of Prevention of Alzheimer’s Disease, 10(3), 595–599. https://doi.org/10.14283/jpad.2023.50
Donanemab for treatment of early Alzheimer’s. (n.d.). Alzheimer’s Association. Retrieved December 17, 2025, from https://www.alz.org/alzheimers-dementia/treatments/donanemab
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. New England Journal of Medicine, 388(1), 9–21. https://doi.org/10.1056/NEJMoa2212948
Fox, N. C., Belder, C., Ballard, C., Kales, H. C., Mummery, C., Caramelli, P., Ciccarelli, O., Frederiksen, K. S., Gomez-Isla, T., Ismail, Z., Paquet, C., Petersen, R. C., Perneczky, R., Robinson, L., Sayin, O., & Frisoni, G. B. (2025). Treatment for Alzheimer’s disease. The Lancet, 406(10510), 1408–1423. https://doi.org/10.1016/S0140-6736(25)01329-7
Gonzales, M. M., Short, M. I., Satizabal, C. L., O’Bryant, S., Tracy, R. P., Zare, H., & Seshadri, S. (2021). Blood biomarkers for dementia in Hispanic and non-Hispanic White adults. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 7(1), e12164. https://doi.org/10.1002/trc2.12164
Grande, G., Valletta, M., Rizzuto, D., Xia, X., Qiu, C., Orsini, N., Dale, M., Andersson, S., Fredolini, C., Winblad, B., Laukka, E. J., Fratiglioni, L., & Vetrano, D. L. (2025). Blood-based biomarkers of Alzheimer’s disease and incident dementia in the community. Nature Medicine, 31(6), 2027–2035. https://doi.org/10.1038/s41591-025-03605-x
Green, R. C., Cupples, L. A., Go, R., Benke, K. S., Edeki, T., Griffith, P. A., Williams, M., Hipps, Y., Graff-Radford, N., Bachman, D., Farrer, L. A., & MIRAGE Study Group. (2002). Risk of dementia among White and African American relatives of patients with Alzheimer disease. JAMA, 287(3), 329–336. https://doi.org/10.1001/jama.287.3.329
Gueorguieva, I., Willis, B. A., Chua, L., Chow, K., Ernest, C. S., Shcherbinin, S., Ardayfio, P., Mullins, G. R., & Sims, J. R. (2023). Donanemab population pharmacokinetics, amyloid plaque reduction, and safety in participants with Alzheimer’s disease. Clinical Pharmacology & Therapeutics, 113(6), 1258–1267. https://doi.org/10.1002/cpt.2875
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I. L., Schultz, A. P., Sepulcre, J., Becker, J. A., Cosio, D. M. O., Farrell, M., Quiroz, Y. T., Mormino, E. C., Buckley, R. F., Papp, K. V., Amariglio, R. A., Dewachter, I., Ivanoiu, A., Huijbers, W., Hedden, T., Marshall, G. A., Chhatwal, J. P., ... Johnson, K. (2019). Association of amyloid and tau with cognition in preclinical Alzheimer disease. JAMA Neurology, 76(8), 915–924. https://doi.org/10.1001/jamaneurol.2019.1424
Hebert, L. E., Weuve, J., Scherr, P. A., & Evans, D. A. (2013). Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology, 80(19), 1778–1783. https://doi.org/10.1212/WNL.0b013e31828726f5
Honig, L. S., Barakos, J., Dhadda, S., Kanekiyo, M., Reyderman, L., Irizarry, M., Kramer, L. D., Swanson, C. J., & Sabbagh, M. (2023). ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 9(1), e12377. https://doi.org/10.1002/trc2.12377
Honig, L. S., Sabbagh, M. N., van Dyck, C. H., Sperling, R. A., Hersch, S., Matta, A., Giorgi, L., Gee, M., Kanekiyo, M., Li, D., Purcell, D., Dhadda, S., Irizarry, M., & Kramer, L. (2024). Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimer’s Research & Therapy, 16, 105. https://doi.org/10.1186/s13195-024-01441-8
Alzheimer’s Disease International, & Patterson, C. (2018). World Alzheimer report 2018: The state of the art of dementia research: New frontiers. https://www.alzint.org/resource/world-alzheimer-report-2018/
Jack, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., Hansson, O., Ho, C., Jagust, W., McDade, E., Molinuevo, J. L., Okonkwo, O. C., Pani, L., Rafii, M. S., Scheltens, P., Siemers, E., Snyder, H. M., Sperling, R., Teunissen, C. E., & Carrillo, M. C. (2024). Revised criteria for diagnosis and staging of Alzheimer’s disease: Alzheimer’s Association Workgroup. Alzheimer’s & Dementia, 20(8), 5143–5169. https://doi.org/10.1002/alz.13859
Jain, S. K., Stevens, C. M., Margret, J. J., & Levine, S. N. (2024). Alzheimer’s disease: A review of pathology, current treatments, and the potential therapeutic effect of decreasing oxidative stress by combined vitamin D and L-cysteine supplementation. Antioxidants & Redox Signaling, 40(10–12), 663–678. https://doi.org/10.1089/ars.2023.0245
Jansen, I. E., Savage, J. E., Watanabe, K., Bryois, J., Williams, D. M., Steinberg, S., Sealock, J., Karlsson, I. K., Hägg, S., Athanasiu, L., Voyle, N., Proitsi, P., Witoelar, A., Stringer, S., Aarsland, D., Almdahl, I. S., Andersen, F., Bergh, S., Bettella, F., ... Posthuma, D. (2019). Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nature Genetics, 51(3), 404–413. https://doi.org/10.1038/s41588-018-0311-9
Johannesson, M., Söderberg, L., Zachrisson, O., Fritz, N., Kylefjord, H., Gkanatsiou, E., Button, E., Svensson, A.-S., Rachalski, A., Nygren, P., Osswald, G., Lannfelt, L., & Möller, C. (2024). Lecanemab demonstrates highly selective binding to Aβ protofibrils isolated from Alzheimer’s disease brains. Molecular and Cellular Neuroscience, 130, 103949. https://doi.org/10.1016/j.mcn.2024.103949
Jönsson, L., Wimo, A., Handels, R., Johansson, G., Boada, M., Engelborghs, S., Frölich, L., Jessen, F., Kehoe, P. G., Kramberger, M., de Mendonça, A., Ousset, P. J., Scarmeas, N., Visser, P. J., Waldemar, G., & Winblad, B. (2023). The affordability of lecanemab, an amyloid-targeting therapy for Alzheimer’s disease: An EADC-EC viewpoint. The Lancet Regional Health - Europe, 29, 100657. https://doi.org/10.1016/j.lanepe.2023.100657
Ju, Y., & Tam, K. Y. (2021). Pathological mechanisms and therapeutic strategies for Alzheimer’s disease. Neural Regeneration Research, 17(3), 543–549. https://doi.org/10.4103/1673-5374.320970
Kamatham, P. T., Shukla, R., Khatri, D. K., & Vora, L. K. (2024). Pathogenesis, diagnostics, and therapeutics for Alzheimer’s disease: Breaking the memory barrier. Ageing Research Reviews, 101, 102481. https://doi.org/10.1016/j.arr.2024.102481
Karikari, T. K., Ashton, N. J., Brinkmalm, G., Brum, W. S., Benedet, A. L., Montoliu-Gaya, L., Lantero-Rodriguez, J., Pascoal, T. A., Suárez-Calvet, M., Rosa-Neto, P., Blennow, K., & Zetterberg, H. (2022). Blood phospho-tau in Alzheimer disease: Analysis, interpretation, and clinical utility. Nature Reviews Neurology, 18(7), 400–418. https://doi.org/10.1038/s41582-022-00665-2
Karlawish, J. (2011). Addressing the ethical, policy, and social challenges of preclinical Alzheimer disease. Neurology, 77(15), 1487–1493. https://doi.org/10.1212/WNL.0b013e318232ac1a
Kavirajan, H. (2009). Memantine: A comprehensive review of safety and efficacy. Expert Opinion on Drug Safety, 8(1), 89–109. https://doi.org/10.1517/14740330802528420
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
Kinchin, I., Walsh, S., Dinh, R., Kapuwa, M., Kennelly, S. P., Miller, A.-M., Nolan, A., O’Dowd, S., O’Philbin, L., Timmons, S., & Leroi, I. (2024). Dissonance in the face of Alzheimer’s disease breakthroughs: Clinician and lay stakeholder acceptance, concerns and willingness to pay for emerging disease-modifying therapies. The British Journal of Psychiatry, 224(6), 230–236. https://doi.org/10.1192/bjp.2024.24
Kumar, A., & Singh, A. (2015). A review on mitochondrial restorative mechanism of antioxidants in Alzheimer’s disease and other neurological conditions. Frontiers in Pharmacology, 6, 206. https://doi.org/10.3389/fphar.2015.00206
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
Lautenschlager, N. T., Cupples, L. A., Rao, V. S., Auerbach, S. A., Becker, R., Burke, J., Chui, H., Duara, R., Foley, E. J., Glatt, S. L., Green, R. C., Jones, R., Karlinsky, H., Kukull, W. A., Kurz, A., Larson, E. B., Martelli, K., Sadovnick, A. D., Volicer, L., ... Farrer, L. A. (1996). Risk of dementia among relatives of Alzheimer’s disease patients in the MIRAGE study: What is in store for the oldest old? Neurology, 46(3), 641–650. https://doi.org/10.1212/WNL.46.3.641
Lecanemab approved for treatment of early Alzheimer’s. (n.d.). Alzheimer’s Association. Retrieved December 17, 2025, from https://www.alz.org/alzheimers-dementia/treatments/lecanemab-leqembi
Liu, C.-C., Kanekiyo, T., Xu, H., & Bu, G. (2013). Apolipoprotein E and Alzheimer disease: Risk, mechanisms, and therapy. Nature Reviews Neurology, 9(2), 106–118. https://doi.org/10.1038/nrneurol.2012.263
Logovinsky, V., Satlin, A., Lai, R., Swanson, C., Kaplow, J., Osswald, G., Basun, H., & Lannfelt, L. (2016). Safety and tolerability of BAN2401—A clinical study in Alzheimer’s disease with a protofibril selective Aβ antibody. Alzheimer’s Research & Therapy, 8(1), 14. https://doi.org/10.1186/s13195-016-0181-2
Long, J. M., & Holtzman, D. M. (2019). Alzheimer disease: An update on pathobiology and treatment strategies. Cell, 179(2), 312–339. https://doi.org/10.1016/j.cell.2019.09.001
Lord, A., Gumucio, A., Englund, H., Sehlin, D., Sundquist, V. S., Söderberg, L., Möller, C., Gellerfors, P., Lannfelt, L., Pettersson, F. E., & Nilsson, L. N. G. (2009). An amyloid-β protofibril-selective antibody prevents amyloid formation in a mouse model of Alzheimer’s disease. Neurobiology of Disease, 36(3), 425–434. https://doi.org/10.1016/j.nbd.2009.08.007
Lowe, S. L., Willis, B. A., Hawdon, A., Natanegara, F., Chua, L., Foster, J., Shcherbinin, S., Ardayfio, P., & Sims, J. R. (2021). Donanemab (LY3002813) dose-escalation study in Alzheimer’s disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 7(1), e12112. https://doi.org/10.1002/trc2.12112
Massoud, F., & Léger, G. C. (2011). Pharmacological treatment of Alzheimer disease. The Canadian Journal of Psychiatry, 56(10), 579–588. https://doi.org/10.1177/070674371105601003
Nelson, P. T., Head, E., Schmitt, F. A., Davis, P. R., Neltner, J. H., Jicha, G. A., Abner, E. L., Smith, C. D., Van Eldik, L. J., Kryscio, R. J., & Scheff, S. W. (2011). Alzheimer’s disease is not “brain aging”: Neuropathological, genetic, and epidemiological human studies. Acta Neuropathologica, 121(5), 571–587. https://doi.org/10.1007/s00401-011-0826-y
Patient dosing & monitoring. (n.d.). KisunlaTM (donanemab-azbt). Retrieved December 17, 2025, from https://kisunla.lilly.com/hcp/dosing-monitoring
Quiroz, Y. T., Zetterberg, H., Reiman, E. M., Chen, Y., Su, Y., Fox-Fuller, J. T., Garcia, G., Villegas, A., Sepulveda-Falla, D., Villada, M., Arboleda-Velasquez, J. F., Guzmán-Vélez, E., Vila-Castelar, C., Gordon, B. A., Schultz, S. A., Protas, H. D., Ghisays, V., Giraldo, M., Tirado, V., ... Lopera, F. (2020). Plasma neurofilament light chain in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: A cross-sectional and longitudinal cohort study. The Lancet Neurology, 19(6), 513–521. https://doi.org/10.1016/S1474-4422(20)30137-X
Rhodius-Meester, H. F. M., Tijms, B. M., Lemstra, A. W., Prins, N. D., Pijnenburg, Y. A. L., Bouwman, F., Scheltens, P., & van der Flier, W. M. (2019). Survival in memory clinic cohort is short, even in young-onset dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 90(6), 726–728. https://doi.org/10.1136/jnnp-2018-318820
Rizoska, B., Zachrisson, O., Appelkvist, P., Boström, E., Björklund, M., Rachalski, A., Gkanatsiou, E., Kylefjord, H., Söderberg, L., Nygren, P., Eriksson, F., Ishikawa, Y., Fukushima, T., Koyama, A., Osswald, G., Lannfelt, L., & Möller, C. (2024). Disease modifying effects of the amyloid-beta protofibril-selective antibody mAb158 in aged Tg2576 transgenic mice. Molecular and Cellular Neuroscience, 130, 103950. https://doi.org/10.1016/j.mcn.2024.103950
Salloway, S., Lee, E., Papka, M., Pain, A., Oru, E., Ferguson, M. B., Wang, H., Case, M., Lu, M., Collins, E. C., Brooks, D. A., & Sims, J. (2023). TRAILBLAZER-ALZ 4: Topline study results directly comparing donanemab to aducanumab on amyloid lowering in early, symptomatic Alzheimer’s disease. BJPsych Open, 9(Suppl. 1), S67. https://doi.org/10.1192/bjo.2023.227
Satlin, A., Wang, J., Logovinsky, V., Berry, S., Swanson, C., Dhadda, S., & Berry, D. A. (2016). 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, 2(1), 1–12. https://doi.org/10.1016/j.trci.2016.01.001
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021). Alzheimer’s disease. The Lancet, 397(10284), 1577–1590. https://doi.org/10.1016/S0140-6736(20)32205-4
Shcherbinin, S., Evans, C. D., Lu, M., Andersen, S. W., Pontecorvo, M. J., Willis, B. A., Gueorguieva, I., Hauck, P. M., Brooks, D. A., Mintun, M. A., & Sims, J. R. (2022). Association of amyloid reduction after donanemab treatment with tau pathology and clinical outcomes. JAMA Neurology, 79(10), 1015–1024. https://doi.org/10.1001/jamaneurol.2022.2793
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., Apostolova, L. G., Hansson, O., Ritchie, C., Brooks, D. A., Mintun, M., & Skovronsky, D. M. (2023). Donanemab in early symptomatic Alzheimer disease. JAMA, 330(6), 512–527. https://doi.org/10.1001/jama.2023.13239
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., Apostolova, L. G., Hansson, O., Ritchie, C., Brooks, D. A., Mintun, M., Skovronsky, D. M., ... Zboch, M. (2023). Donanemab in early symptomatic Alzheimer disease: The TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA, 330(6), 512. https://doi.org/10.1001/jama.2023.13239
Singh, P. K., Simões-Pires, E. N., Chen, Z.-L., Torrente, D., Calvano, M., Sharma, A., Strickland, S., & Norris, E. H. (n.d.). Lecanemab blocks the effects of the Aβ/fibrinogen complex on blood clots and synapse toxicity in organotypic culture. Proceedings of the National Academy of Sciences of the United States of America, 121(17), e2314450121. https://doi.org/10.1073/pnas.2314450121
Soni, U., Singh, K., Jain, D., & Pujari, R. (2025). Exploring Alzheimer’s disease treatment: Established therapies and novel strategies for future care. European Journal of Pharmacology, 998, 177520. https://doi.org/10.1016/j.ejphar.2025.177520
Sperling, R., Salloway, S., Brooks, D. J., Tampieri, D., Barakos, J., Fox, N. C., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Lieberburg, I., Arrighi, H. M., Morris, K. A., Lu, Y., Liu, E., Gregg, K. M., Brashear, R. H., Kinney, G. G., Black, R., & Grundman, M. (2012). Amyloid-related imaging abnormalities (ARIA) in Alzheimer’s disease patients treated with bapineuzumab: A retrospective analysis. The Lancet Neurology, 11(3), 241–249. https://doi.org/10.1016/S1474-4422(12)70015-7
Swanson, C. J., Zhang, Y., Dhadda, S., Wang, J., Kaplow, J., Lai, R. Y. K., Lannfelt, L., Bradley, H., Rabe, M., Koyama, A., Reyderman, L., Berry, D. A., Berry, S., Gordon, R., Kramer, L. D., & Cummings, J. L. (2021). 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, 13, 80. https://doi.org/10.1186/s13195-021-00813-8
Tamagno, E., Guglielmotto, M., Aragno, M., Borghi, R., Autelli, R., Giliberto, L., Muraca, G., Danni, O., Zhu, X., Smith, M. A., Perry, G., Jo, D.-G., Mattson, M. P., & Tabaton, M. (2008). Oxidative stress activates a positive feedback between the γ- and β-secretase cleavages of the β-amyloid precursor protein. Journal of Neurochemistry, 104(3), 683–695. https://doi.org/10.1111/j.1471-4159.2007.05072.x
Terao, I., & Kodama, W. (2024). Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer’s disease: A systematic review and network meta-analysis. Ageing Research Reviews, 94, 102203. https://doi.org/10.1016/j.arr.2024.102203
TRAILBLAZER-ALZ 5. (n.d.). Retrieved December 16, 2025, from https://www.alzheimer-europe.org/research/clinical-trials/trailblazer-alz-5?language_content_entity=en
Tucker, S., Möller, C., Tegerstedt, K., Lord, A., Laudon, H., Sjödahl, J., Söderberg, L., Spens, E., Sahlin, C., Waara, E. R., Satlin, A., Gellerfors, P., Osswald, G., & Lannfelt, L. (2015). 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, 43(2), 575–588. https://doi.org/10.3233/JAD-140741
U.S. Food and Drug Administration. (2023). Lecanemab (BAN2401) FDA briefing document. https://www.fda.gov/media/169264/download
U.S. Food and Drug Administration. (2024, June 10). Donanemab peripheral and central nervous system drugs advisory committee June 10, 2024. FDA. https://www.fda.gov/advisory-committees/advisory-committee-calendar/updated-public-participation-information-june-10-2024-meeting-peripheral-and-central-nervous-system
van der Lee, S. J., Wolters, F. J., Ikram, M. K., Hofman, A., Ikram, M. A., Amin, N., & van Duijn, C. M. (2018). The effect of APOE and other common genetic variants on the onset of Alzheimer’s disease and dementia: A community-based cohort study. The Lancet Neurology, 17(5), 434–444. https://doi.org/10.1016/S1474-4422(18)30053-X
van Olst, L., Simonton, B., Edwards, A. J., Forsyth, A. V., Boles, J., Jamshidi, P., Watson, T., Shepard, N., Krainc, T., Argue, B. M., Zhang, Z., Kuruvilla, J., Camp, L., Li, M., Xu, H., Norman, J. L., Cahan, J., Vassar, R., Chen, J., ... Gate, D. (2025). Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease. Nature Medicine, 31(5), 1604–1616. https://doi.org/10.1038/s41591-025-03574-1
Vukmir, R. B. (2024). Amyloid-related imaging abnormalities (ARIA): Diagnosis, management, and care in the setting of amyloid-modifying therapy. Annals of Clinical and Translational Neurology, 11(7), 1669–1680. https://doi.org/10.1002/acn3.52042
Wang, H., Nery, E. S. M., Ardayfio, P., Khanna, R., Svaldi, D. O., Shcherbinin, S., Xu, W., Andersen, S. W., Hauck, P. M., Brooks, D. A., Collins, E. C., Salloway, S., Mintun, M. A., & Sims, J. R. (2025). The effect of modified donanemab titration on amyloid-related imaging abnormalities with edema/effusions and amyloid reduction: 18-month results from TRAILBLAZER-ALZ 6. The Journal of Prevention of Alzheimer’s Disease, 12(8), Article 100266. https://doi.org/10.1016/j.tjpad.2025.100266
Whitehouse, P. J. (2019). Ethical issues in early diagnosis and prevention of Alzheimer disease. Dialogues in Clinical Neuroscience, 21(1), 101–108. https://doi.org/10.31887/DCNS.2019.21.1/pwhitehouse
Wright, A. L., Zinn, R., Hohensinn, B., Konen, L. M., Beynon, S. B., Tan, R. P., Clark, I. A., Abdipranoto, A., & Vissel, B. (2013). Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer’s disease. PLoS ONE, 8(4), e59586. https://doi.org/10.1371/journal.pone.0059586
Yaari, R., Holdridge, K. C., Williamson, M., Wessels, A. M., Shcherbinin, S., Kotari, V., Reiman, E. M., Tariot, P. N., Alexander, R., Langbaum, J. B., & Sims, J. R. (2025). Donanemab in preclinical Alzheimer’s disease: Screening and baseline data from TRAILBLAZER-ALZ 3. Alzheimer’s & Dementia, 21(9), e70662. https://doi.org/10.1002/alz.70662
Zhang, X.-X., Tian, Y., Wang, Z.-T., Ma, Y.-H., Tan, L., & Yu, J.-T. (2021). The epidemiology of Alzheimer’s disease modifiable risk factors and prevention. The Journal of Prevention of Alzheimer’s Disease, 8(3), 313–321. https://doi.org/10.14283/jpad.2021.15
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Copyright (c) 2026 Karolina Ollik, Kamil Harenza, Mateusz Taranowicz, Olga Kowalczyk, Dominika Zdobylak, Monika Kowalska, Anita Zięba, Michał Domin, Justyna Całka, Katarzyna Ścibisz
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