98% of small molecules and 100% of large molecules do not cross the blood-brain barrier (BBB). Biologics, including therapeutic antibodies (e.g. anti-amyloid antibodies), have been at the forefront of Alzheimer’s disease (AD) research, however have had limited success so far. Biologics are large molecules with limited permeability across the BBB, and in the absence of a BBB-targeting approach to deliver these biologics to the brain, the true potential of the biologic cannot be determined. One approach to deliver a biologic, including anti-amyloid antibodies, decoy receptors and neurotrophins, for AD is to engineer bispecific fusion proteins, such that one domain of the fusion protein is the therapeutic biologic of interest, and the other domain acts as a molecular Trojan horse to ferry the biologic into the brain. This talk will focus on some of our work involving the targeting of the BBB transferrin receptor to deliver biologics (e.g. anti-amyloid antibody and biologic TNF-a inhibitor) in mouse models of AD.