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<p>Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder, the treatment of which remains a major clinical challenge. In recent years, significant progress has been made in the immunotherapy of AD. Notably, monoclonal antibodies targeting amyloid-β (Aβ) have already been applied in clinical practice. However, as macromolecular therapeutics, antibodies face substantial challenges in crossing the blood-brain barrier (BBB) efficiently. Systemic administration typically requires high dosages to achieve the therapeutic level of brain exposure, which may trigger adverse events such as amyloid-related imaging abnormalities (ARIA) and thus restrict their widespread clinical application. To resolve this problem, various engineering strategies for modifying anti-Aβ antibodies have been developed. This review summarizes four major modification categories: BBB-penetrating bispecific antibodies (BsAbs), glycosylation engineering, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR)-based cell therapies (including CAR-macrophages, CAR-T cells, and CAR-astrocytes). We provide an in-depth discussion of their delivery efficiency, targeting capability, and safety, aiming to lay a foundation for developing safer and more effective next-generation anti-Aβ antibody therapeutic strategies.</p>

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Advances in modified anti-Aβ antibodies for the treatment of Alzheimer’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Shuang Li,
  • Jiwei Gu,
  • Zucai Xu,
  • Chunyang He,
  • Changyin Yu

摘要

Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder, the treatment of which remains a major clinical challenge. In recent years, significant progress has been made in the immunotherapy of AD. Notably, monoclonal antibodies targeting amyloid-β (Aβ) have already been applied in clinical practice. However, as macromolecular therapeutics, antibodies face substantial challenges in crossing the blood-brain barrier (BBB) efficiently. Systemic administration typically requires high dosages to achieve the therapeutic level of brain exposure, which may trigger adverse events such as amyloid-related imaging abnormalities (ARIA) and thus restrict their widespread clinical application. To resolve this problem, various engineering strategies for modifying anti-Aβ antibodies have been developed. This review summarizes four major modification categories: BBB-penetrating bispecific antibodies (BsAbs), glycosylation engineering, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR)-based cell therapies (including CAR-macrophages, CAR-T cells, and CAR-astrocytes). We provide an in-depth discussion of their delivery efficiency, targeting capability, and safety, aiming to lay a foundation for developing safer and more effective next-generation anti-Aβ antibody therapeutic strategies.