title: Conformation-specific antibodies to target amyloid β oligomers and their application to immunotherapy for Alzheimer's disease.
abstract: Amyloid β-protein (Aβ) oligomers, intermediates of Aβ aggregation, cause cognitive impairment and synaptotoxicity in the pathogenesis of Alzheimer's disease (AD). Immunotherapy using anti-Aβ 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 Aβ as well as the pathological oligomers by these antibodies that recognize Aβ sequence, which is not involved in synaptotoxicity. Several efforts have been made recently to develop conformation-specific antibodies that target the tertiary structure of Aβ oligomers. Here, we review the recent findings of Aβ oligomers and anti-Aβ antibodies including our own, and discuss their potential as therapeutic and diagnostic tools.
authors.affiliation: a Division of Food Science and Biotechnology , Graduate School of Agriculture, Kyoto University , Kyoto , Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Murakami
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D000918:Antibody Specificity; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies
keywords: Alzheimer’s disease; amyloid β; antibody; conformation; oligomer