title: Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers.
abstract: Increasing evidence indicates that beta-amyloid (Abeta) oligomers rather than monomers or fibrils are the major toxic agents that specifically inhibit synaptic plasticity and long-term potentiation (LTP) in Alzheimer's disease (AD). Neutralization of Abeta oligomeric toxicity was found to reverse memory deficits. Here, we report four single-chain variable fragment (scFv) antibodies isolated from the naive human scFv library by phage display that specifically recognized Abeta oligomers but not monomers and fibrils. These conformation-dependent scFv antibodies inhibit both Abeta fibrillation and cytotoxicity and bind to the same type of eptitope displayed on the Abeta oligomers. Such scFv antibodies specifically targeting toxic Abeta oligomers may have potential therapeutic and diagnostic applications for AD.
authors.affiliation: Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Wang
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Zhang
authors.forename: Yu-jiong
authors.initials: YJ
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao-xia
authors.initials: XX
authors.lastname: Sun
authors.forename: Ji-liang
authors.initials: JL
authors.lastname: Li
authors.forename: Xue-ting
authors.initials: XT
authors.lastname: Du
authors.forename: Mary P
authors.initials: MP
authors.lastname: Lambert
authors.forename: Shi-gao
authors.initials: SG
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D000682:Amyloid / Q000276:immunology* / Q000378:metabolism* / Q000633:toxicity; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D000682:Amyloid; D000906:Antibodies; D000939:Epitopes