Anti-amyloid antibodies achieve only ~0.1% brain penetrance via passive diffusion, limiting efficacy. Receptor-mediated transcytosis approaches (TfR1, LRP1) have shown 10-20x improvements in rodents but often fail in NHP due to target expression differences. Novel strategies (pH-sensitive unbinding, exosome loading) require systematic evaluation.
Anti-amyloid antibodies (lecanemab, donanemab) have ~0.1% brain penetrance. Engineering improved BBB transcytosis via transferrin receptor, LRP1, or novel shuttle peptides could dramatically improve efficacy.