Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers.
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.
Wang
Xiao-ping
XP
Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China.
Zhang
Jun-hua
JH
Wang
Yu-jiong
YJ
Feng
Ying
Y
Zhang
Xi
X
Sun
Xiao-xia
XX
Li
Ji-liang
JL
Du
Xue-ting
XT
Lambert
Mary P
MP
Yang
Shi-gao
SG
Zhao
Min
M
Klein
William L
WL
Liu
Rui-tian
RT
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
D000682:Amyloid; D000906:Antibodies; D000939:Epitopes