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.