Overview

• ATVcisLALA leverages transferrin receptor–mediated transcytosis to deliver anti-amyloid antibodies across the blood–brain barrier in mouse models.
• Asymmetrical Fc cisLALA mutations reduce binding to immune receptors on immature red blood cells, preventing cytotoxic side effects.
• Treated mice maintain robust microglial clearance of amyloid-β plaques, preserving key immune functions.
• Preferential targeting of parenchymal plaque deposits over vascular amyloid cuts inflammation and nearly eradicates ARIA-like brain swelling and microbleeds.
• The study outlines a design framework for next-generation Alzheimer’s immunotherapies with enhanced efficacy and safety for clinical translation.