Document Type
Article
Publication Date
4-16-2026
Abstract
Antibodies directed against β-amyloid (Aβ) have been developed for the treatment of Alzheimer’s disease (AD). However, the in vivo central efficacy is reduced by the poor penetration of antibodies across the blood–brain barrier (BBB). In addition, these antibodies have been associated with adverse effects like amyloid-related imaging abnormalities. Thus, the development of new antibody-based therapies for AD with improved transport across the BBB may improve efficacy and reduce adverse effects. Antibodies targeting the BBB transferrin receptor (TfR) are able to cross the BBB through receptor-mediated transcytosis, producing a global distribution throughout the brain. Along the same line, bispecific antibodies directed to both the BBB TfR and Aβ showed enhanced brain uptake and pharmacological effects with diminished adverse side effects in experimental animal models of AD and in clinical trials. A generation of brain-penetrating fusion proteins targeting the BBB-TfR has been shown to represent novel treatments for AD, and this includes erythropoietin, tumor necrosis factor alpha inhibitors, neprilysin, somatostatin, oligonucleotides, and an antibody activating TREM2. The aim of this article is to review the progress made in the delivery of antibody-derived biologicals to the brain for AD, targeting the BBB-TfR.
Recommended Citation
Sumbria, R.K.; Boado, R.J. Brain Delivery of Antibody-Derived Biologicals for Alzheimer’s Disease: An Updated Narrative Review. Antibodies 2026, 15, 37. https://doi.org/10.3390/antib15020037
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Nervous System Diseases Commons, Pharmaceutics and Drug Design Commons, Therapeutics Commons
Comments
This article was originally published in Antibodies, volume 15, in 2026. https://doi.org/10.3390/antib15020037