Provided are central nervous system (CNS)-targeted antibody or therapeutic Fc-fusion polypeptide conjugates having modified Fc regions, and related methods of use thereof, for instance, to facilitate delivery of therapeutic and/or diagnostic polypeptides across the blood-brain barrier (BBB), and thereby treat and/or diagnose conditions associated with the CNS, including cancer, pain, and various neuropathologies, such as neuroinflammatory, auto-immune, and/or neurodegenerative disorders.
