Advances in modified anti-Aβ antibodies for the treatment of Alzheimer’s disease
- 1Department of Neurology, Affiliated Hospital of Zunyi Medical University
- 2School of Medicine, Yale University
- 3Guizhou Provincial Key Laboratory of Innovation and Manufacturing for Pharmaceuticals, School of Pharmacy, Zunyi Medical University
Abstract
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.
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BibTeX
@article{li2026advances,
title = {{Advances in modified anti-Aβ antibodies for the treatment of Alzheimer’s disease}},
author = {Shuang Li and Jiwei Gu and Zucai Xu and Chunyang He and Changyin Yu},
journal = {BMC Medicine},
year = {2026},
month = jul,
doi = {10.1186/s12916-026-05088-0},
url = {https://doi.org/10.1186/s12916-026-05088-0},
note = {CC BY},
}
RIS
TY - JOUR
TI - Advances in modified anti-Aβ antibodies for the treatment of Alzheimer’s disease
AU - Shuang Li
AU - Jiwei Gu
AU - Zucai Xu
AU - Chunyang He
AU - Changyin Yu
PY - 2026
DA - 2026/07/01
JO - BMC Medicine
DO - 10.1186/s12916-026-05088-0
UR - https://doi.org/10.1186/s12916-026-05088-0
AB - 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.
SN - 1741-7015
ER -