Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives
Abstract Alzheimer’s disease (AD) is the most common type of dementia. Monoclonal antibodies (MABs) serve as a promising therapeutic approach for AD by selectively targeting key pathogenic factors, such as amyloid-β (Aβ) peptide, tau protein, and neuroinflammation. Specifically, based on their effic...
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BMC
2025-01-01
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| Series: | Translational Neurodegeneration |
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| Online Access: | https://doi.org/10.1186/s40035-025-00465-w |
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| author | Byeong-Hyeon Kim Sujin Kim Yunkwon Nam Yong Ho Park Seong Min Shin Minho Moon |
| author_facet | Byeong-Hyeon Kim Sujin Kim Yunkwon Nam Yong Ho Park Seong Min Shin Minho Moon |
| author_sort | Byeong-Hyeon Kim |
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| description | Abstract Alzheimer’s disease (AD) is the most common type of dementia. Monoclonal antibodies (MABs) serve as a promising therapeutic approach for AD by selectively targeting key pathogenic factors, such as amyloid-β (Aβ) peptide, tau protein, and neuroinflammation. Specifically, based on their efficacy in removing Aβ plaques from the brains of patients with AD, the U.S. Food and Drug Administration has approved three anti-amyloid MABs, aducanumab (Aduhelm®), lecanemab (Leqembi®), and donanemab (Kisunla™). Notably, lecanemab received traditional approval after demonstrating clinical benefit, supporting the Aβ cascade hypothesis. These MABs targeting Aβ are categorized based on their affinity to diverse conformational features of Aβ, including monomer, fibril, protofibril, and plaque forms of Aβ as well as pyroglutamate Aβ. First-generation MABs targeting the non-toxic monomeric Aβ, such as solanezumab, bapineuzumab, and crenezumab, failed to demonstrate clinical benefit for AD in clinical trials. In contrast, second-generation MABs, including aducanumab, lecanemab, donanemab, and gantenerumab directed against pathogenic Aβ species and aggregates have shown that reducing Aβ deposition can be an effective strategy to slow cognitive impairment in AD. In this review, we provide a comprehensive overview of the current status, mechanisms, outcomes, and limitations of second-generation MABs for the clinical treatment of AD. Moreover, we discuss the perspectives and future directions of anti-amyloid MABs in the treatment of AD. |
| format | Article |
| id | doaj-art-0411917ba1c245a6829745526b790a56 |
| institution | Kabale University |
| issn | 2047-9158 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj-art-0411917ba1c245a6829745526b790a562025-02-02T12:40:05ZengBMCTranslational Neurodegeneration2047-91582025-01-0114111910.1186/s40035-025-00465-wSecond-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectivesByeong-Hyeon Kim0Sujin Kim1Yunkwon Nam2Yong Ho Park3Seong Min Shin4Minho Moon5Department of Biochemistry, College of Medicine, Konyang UniversityDepartment of Biochemistry, College of Medicine, Konyang UniversityDepartment of Biochemistry, College of Medicine, Konyang UniversityDepartment of Biochemistry, College of Medicine, Konyang UniversityDepartment of Biochemistry, College of Medicine, Konyang UniversityDepartment of Biochemistry, College of Medicine, Konyang UniversityAbstract Alzheimer’s disease (AD) is the most common type of dementia. Monoclonal antibodies (MABs) serve as a promising therapeutic approach for AD by selectively targeting key pathogenic factors, such as amyloid-β (Aβ) peptide, tau protein, and neuroinflammation. Specifically, based on their efficacy in removing Aβ plaques from the brains of patients with AD, the U.S. Food and Drug Administration has approved three anti-amyloid MABs, aducanumab (Aduhelm®), lecanemab (Leqembi®), and donanemab (Kisunla™). Notably, lecanemab received traditional approval after demonstrating clinical benefit, supporting the Aβ cascade hypothesis. These MABs targeting Aβ are categorized based on their affinity to diverse conformational features of Aβ, including monomer, fibril, protofibril, and plaque forms of Aβ as well as pyroglutamate Aβ. First-generation MABs targeting the non-toxic monomeric Aβ, such as solanezumab, bapineuzumab, and crenezumab, failed to demonstrate clinical benefit for AD in clinical trials. In contrast, second-generation MABs, including aducanumab, lecanemab, donanemab, and gantenerumab directed against pathogenic Aβ species and aggregates have shown that reducing Aβ deposition can be an effective strategy to slow cognitive impairment in AD. In this review, we provide a comprehensive overview of the current status, mechanisms, outcomes, and limitations of second-generation MABs for the clinical treatment of AD. Moreover, we discuss the perspectives and future directions of anti-amyloid MABs in the treatment of AD.https://doi.org/10.1186/s40035-025-00465-wAlzheimer’s diseaseAducanumabLecanemabDonanemabGantenerumabAmyloid-related imaging abnormalities |
| spellingShingle | Byeong-Hyeon Kim Sujin Kim Yunkwon Nam Yong Ho Park Seong Min Shin Minho Moon Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives Translational Neurodegeneration Alzheimer’s disease Aducanumab Lecanemab Donanemab Gantenerumab Amyloid-related imaging abnormalities |
| title | Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives |
| title_full | Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives |
| title_fullStr | Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives |
| title_full_unstemmed | Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives |
| title_short | Second-generation anti-amyloid monoclonal antibodies for Alzheimer’s disease: current landscape and future perspectives |
| title_sort | second generation anti amyloid monoclonal antibodies for alzheimer s disease current landscape and future perspectives |
| topic | Alzheimer’s disease Aducanumab Lecanemab Donanemab Gantenerumab Amyloid-related imaging abnormalities |
| url | https://doi.org/10.1186/s40035-025-00465-w |
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