Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers

Wang, Xiao-ping; Zhang, Jun-hua; Wang, Yu-jiong; Feng, Ying; Zhang, Xi; Sun, Xiao-xia; Li, Ji-liang; Du, Xue-ting; Lambert, Mary P.; Yang, Shi-gao; Zhao, Min; Klein, William L.; Liu, Rui-tian

doi:10.1016/j.febslet.2008.12.064

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Volume 583, Issue 3 , Pages 579-584, 4 February 2009

Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers

Edited by Jesus Avila

Xiao-ping Wang
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
- School of Life Science, Ningxia University, Yinchuan 750021, China
- These authors contributed equally to this work.
Jun-hua Zhang
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
- School of Life Science, Ningxia University, Yinchuan 750021, China
- These authors contributed equally to this work.
Yu-jiong Wang
- School of Life Science, Ningxia University, Yinchuan 750021, China
- These authors contributed equally to this work.
Ying Feng
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
Xi Zhang
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
Xiao-xia Sun
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
Ji-liang Li
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
- School of Life Science, Ningxia University, Yinchuan 750021, China
Xue-ting Du
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
- School of Life Science, Ningxia University, Yinchuan 750021, China
Mary P. Lambert
- Department of Neurobiology and Physiology, Northwestern University, Evanston, IL, USA
Shi-gao Yang
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
Min Zhao
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
William L. Klein
- Department of Neurobiology and Physiology, Northwestern University, Evanston, IL, USA
Rui-tian Liu
- Tsinghua University, School of Medicine, Haidian District, Beijing 100084, China
- Corresponding author. Fax: +86 010 62792995.

Received 25 November 2008; received in revised form 19 December 2008; accepted 30 December 2008. published online 21 January 2009.

Abstract

Increasing evidence indicates that beta-amyloid (Aβ) 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 Aβ 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 Aβ oligomers but not monomers and fibrils. These conformation-dependent scFv antibodies inhibit both Aβ fibrillation and cytotoxicity and bind to the same type of eptitope displayed on the Aβ oligomers. Such scFv antibodies specifically targeting toxic Aβ oligomers may have potential therapeutic and diagnostic applications for AD.

Keywords: Alzheimer’s disease, Beta-amyloid, Oligomer, Epitope, Single-chain variable fragment

Abbreviations: AD, Alzheimer’s disease, Aβ, beta-amyloid peptide, scFv, single-chain variable fragment, SPR, surface plasmon resonance, SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, LDH, lactate dehydrogenase, MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, ADDL, amyloid β-derived diffusible ligand