title: Modulators of IgG penetration through the blood-brain barrier: Implications for Alzheimer's disease immunotherapy.
abstract: This review serves to highlight approaches that may improve the access of antibody drugs to regions of the brain affected by Alzheimer's Disease. While previous antibody drugs have been unsuccessful in treating Alzheimer's disease, recent work demonstrates that Alzheimer's pathology can be modified if these drugs can penetrate the brain parenchyma with greater efficacy. Research in antibody blood-brain barrier drug delivery predominantly follows one of three distinct directions: (1) enhancing influx with reduced antibody size, addition of Trojan horse modules, or blood-brain barrier disruption; (2) modulating trancytotic equilibrium and/or kinetics of the neonatal Fc Receptor; and (3) manipulation of antibody glycan carbohydrate composition. In addition to these topics, recent studies are discussed that reveal a role of glycan sialic acid in suppressing antibody efflux from the brain.
authors.affiliation: Division of Sciences and Mathematics, Interdisciplinary Arts and Sciences, University of Washington Tacoma, Tacoma, WA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Finke
authors.affiliation: Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.|Department of Geriatric Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Banks
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002236:Carbohydrate Conformation; D005786:Gene Expression Regulation / Q000187:drug effects; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000096:biosynthesis / Q000235:genetics; D007167:Immunotherapy / Q000379:methods*; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000276:immunology; D015202:Protein Engineering / Q000379:methods; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D019158:N-Acetylneuraminic Acid; C100688:Fc receptor, neonatal
keywords: Alzheimer's disease; Blood-brain barrier; FcRn; IgG; antibody; beta-amyloid; glycosylation; sialic acid