Single chain variable fragments against β-amyloid (Aβ) can inhibit Aβ aggregation and prevent Aβ-induced neurotoxicity

Ruitian Liu, Bin Yuan, Sharareh Emadi, Andleeb Zameer, Philip Schulz, Chad McAllister, Yuri Lyubchenko, Gaddam Goud, Michael Sierks

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103 Scopus citations

Abstract

β-Amyloid (Aβ) is a major pathological determinant of Alzheimer's disease (AD). Both active and passive immunization studies have shown that antibodies against Aβ are effective in decreasing cerebral Aβ levels, reducing Aβ accumulation, and attenuating cognitive deficits in animal models of AD. However, the therapeutic potential of these antibodies in human AD patients is limited because of adverse inflammatory reactions and cerebral hemorrhaging associated with the treatments. Here we show that single chain variable fragments (scFv's) represent an attractive alternative to more conventional antibody-based therapeutics to reduce Aβ toxicity. The binding affinities and binding epitopes of two different scFv's to Aβ were characterized using a surface plasmon resonance (SPR) biosensor. An scFv binding the 17-28 region of Aβ effectively inhibited in vitro aggregation of Aβ as determined by thioflavin T (ThT) fluorescence staining and atomic force microscopy (AFM) analysis, while an scFv binding the carboxyl-terminal region of Aβ (residues 29-40) did not inhibit aggregation. The scFv to the 17-28 region when co-incubated with Aβ not only decreased aggregation but also eliminated any toxic effects of aggregated Aβ on the human neuroblastoma cell line, SH-SY5Y. The ability of scFv's to inhibit both aggregation and cytotoxicity of Aβ indicates that scFv's have potential therapeutic value for treating AD.

Original languageEnglish (US)
Pages (from-to)6959-6967
Number of pages9
JournalBiochemistry
Volume43
Issue number22
DOIs
StatePublished - Jun 8 2004

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Liu, R., Yuan, B., Emadi, S., Zameer, A., Schulz, P., McAllister, C., Lyubchenko, Y., Goud, G., & Sierks, M. (2004). Single chain variable fragments against β-amyloid (Aβ) can inhibit Aβ aggregation and prevent Aβ-induced neurotoxicity. Biochemistry, 43(22), 6959-6967. https://doi.org/10.1021/bi049933o