title: Monoclonal antibody with conformational specificity for a toxic conformer of amyloid β42 and its application toward the Alzheimer's disease diagnosis.
abstract: Amyloid β-protein (Aβ42) oligomerization is an early event in Alzheimer's disease (AD). Current diagnostic methods using sequence-specific antibodies against less toxic fibrillar and monomeric Aβ42 run the risk of overdiagnosis. Hence, conformation-specific antibodies against neurotoxic Aβ42 oligomers have garnered much attention for developing more accurate diagnostics. Antibody 24B3, highly specific for the toxic Aβ42 conformer that has a turn at Glu22 and Asp23, recognizes a putative Aβ42 dimer, which forms stable and neurotoxic oligomers more potently than the monomer. 24B3 significantly rescues Aβ42-induced neurotoxicity, whereas sequence-specific antibodies such as 4G8 and 82E1, which recognizes the N-terminus, do not. The ratio of toxic to total Aβ42 in the cerebrospinal fluid of AD patients is significantly higher than in control subjects as measured by sandwich ELISA using antibodies 24B3 and 82E1. Thus, 24B3 may be useful for AD diagnosis and therapy.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Tokuda
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Irie
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hanaki
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Izuo
authors.affiliation: National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Monobe
authors.affiliation: National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Akagi
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Ishii
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Harutsugu
authors.initials: H
authors.lastname: Tatebe
authors.affiliation: Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, Japan.|Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Tokuda
authors.affiliation: Immuno-Biological Laboratories Co, Ltd., Gunma, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000134:cerebrospinal fluid* / Q000737:chemistry; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008968:Molecular Conformation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000633:toxicity; D017208:Rats, Wistar; D020349:Surface Plasmon Resonance
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)