Conformation-specific antibodies to target amyloid β oligomers and their application to immunotherapy for Alzheimer's disease

Amyloid beta-protein (A beta) oligomers, intermediates of A beta aggregation, cause cognitive impairment and synaptotoxicity in the pathogenesis of Alzheimer's disease (AD). Immunotherapy using anti-A beta antibody is one of the most promising approaches for AD treatment. However, most clinical trials using conventional sequence-specific antibodies have proceeded with difficulty. This is probably due to the unintended removal of the non-pathological monomer and fibrils of A beta as well as the pathological oligomers by these antibodies that recognize A beta sequence, which is not involved in synaptotoxicity. Several efforts have been made recently to develop conformation-specific antibodies that target the tertiary structure of A beta oligomers. Here, we review the recent findings of A beta oligomers and anti-A beta antibodies including our own, and discuss their potential as therapeutic and diagnostic tools.