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

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

doi:10.1016/j.febslet.2008.12.064

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

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

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

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.

Original language	English (US)
Pages (from-to)	579-584
Number of pages	6
Journal	FEBS Letters
Volume	583
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2008.12.064
State	Published - Feb 4 2009

Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (30570622), the Natural Science Foundation of Beijing, China (5072023), the National High Technology Research and Development Program of China (863 Program) (No. 2007AA02Z309), Dr Shun Tak Wu’s Medical Sciences Fund and Tsinghua-Yue-Yuen Medical Sciences Fund. We are grateful to Dr. Minghui Zhang, Dr. Fanglin Sun and Dr. Charles G. Glabe for technical assistance.

Keywords

Alzheimer's disease
Beta-amyloid
Epitope
Oligomer
Single-chain variable fragment

ASJC Scopus subject areas

Genetics
Molecular Biology
Biophysics
Structural Biology
Biochemistry
Cell Biology

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10.1016/j.febslet.2008.12.064

Cite this

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title = "Conformation-dependent single-chain variable fragment antibodies specifically recognize beta-amyloid oligomers",

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, Epitope, Oligomer, Single-chain variable fragment",

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

note = "Funding Information: This work was supported by grants from the National Natural Science Foundation of China (NSFC) (30570622), the Natural Science Foundation of Beijing, China (5072023), the National High Technology Research and Development Program of China (863 Program) (No. 2007AA02Z309), Dr Shun Tak Wu{\textquoteright}s Medical Sciences Fund and Tsinghua-Yue-Yuen Medical Sciences Fund. We are grateful to Dr. Minghui Zhang, Dr. Fanglin Sun and Dr. Charles G. Glabe for technical assistance.",

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AU - Wang, Xiao ping

AU - Zhang, Jun hua

AU - Wang, Yu jiong

AU - Feng, Ying

AU - Zhang, Xi

AU - Sun, Xiao xia

AU - Li, Ji liang

AU - Du, Xue ting

AU - Lambert, Mary P.

AU - Yang, Shi gao

AU - Zhao, Min

AU - Klein, William L.

AU - Liu, Rui tian

N1 - Funding Information: This work was supported by grants from the National Natural Science Foundation of China (NSFC) (30570622), the Natural Science Foundation of Beijing, China (5072023), the National High Technology Research and Development Program of China (863 Program) (No. 2007AA02Z309), Dr Shun Tak Wu’s Medical Sciences Fund and Tsinghua-Yue-Yuen Medical Sciences Fund. We are grateful to Dr. Minghui Zhang, Dr. Fanglin Sun and Dr. Charles G. Glabe for technical assistance.

PY - 2009/2/4

Y1 - 2009/2/4

N2 - 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.

AB - 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.

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KW - Oligomer

KW - Single-chain variable fragment

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

Abstract

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Keywords

ASJC Scopus subject areas

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