Antibody-mediated immunotherapy for Alzheimer's disease.
Immunotherapy against beta-amyloid (Abeta) peptide in transgenic mouse models of Alzheimer's disease alleviates the amyloid-associated pathology via three distinct mechanisms. First, antibodies directed against the N-terminal region of Abeta plaques leads to the dissolution of Abeta in the CNS. Second, opsonization of amyloid by an antibody occurs and is thus cleared via Fc-dependent phagocytosis. However, both of these mechanisms require the entry of antibodies into the CNS. Conversely, the third mechanism involves the sequestering of plasma Abeta by antibodies, establishing a gradient favoring the efflux of Abeta from the CNS, and is thus not dependent upon the translocation of antibodies across the blood-brain barrier. Clearly, future therapeutic approaches for Alzheimer's disease depend on increased research into the various mechanisms of immunotherapy to successfully clear Abeta peptides.
Tel-Aviv University, George S Wise Faculty of Life Sciences, Department of Molecular Microbiology & Biotechnology, Ramat Aviv, Tel-Aviv 69978, Israel. beka@post.tau.ac.il
Beka
B
Solomon
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008954:Models, Biological
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal