The invention relates to a method for brain targeted delivery of macromolecular protein or peptide ligands, including mono- or bispecific antibodies, nanobodies and active ingredients possessing specificity for 45 to 384 amino acid region of the SDC3 core protein into the brain, by a.) attaching the mono- or bispecific SDC3 antibody, nanobody, or mono or bispecific macromolecular ligands via systemic circulation to 45 to 384 amino acid region of SDC3 expressed on endothelial cells of the blood-brain-barrier, or b.) conjugating an active ingredient to an SDC3 specific mono- or bispecific antibody, nanobody, or mono or bispecific macromolecular ligands, and attaching the conjugate via systemic circulation to SDC3 expressed by endothelial cells of the blood-brain-barrier. Furtheron the invention relates to the use of a syndecan-3 target antibody, nanobody or macromolecular ligand, alone or in association with an active ingredient, as a therapeutic agent for treating neurodegenerative or metabolic disorders.