Shuttle systems for delivering antibody therapeutics across the BBB for the treatment of Alzheimer’s disease

Antibodies are emerging as a promising drug modality for Alzheimer’s Disease. Yet the clinical success of these therapies is, in part, limited by their inability to cross the blood–brain barrier (BBB). Multiple delivery strategies have been attempted to enable antibody therapeutics to bypass or cross the BBB; incorporating components that target transcytosis receptors on brain endothelial cells (BECs) remains a top approach. In this review, we focus on BBB shuttle technologies targeting the transferrin receptor (TfR), insulin receptor (IR), neonatal Fc receptor (FcRn), and CD98 heavy chain (CD98hc), emphasizing their distinct advantages. Incorporating these BBB shuttle technologies into the next generation of AD antibody therapeutics will improve brain penetration and, consequently, clinical efficacy.