Characterization of a single-chain variable fragment recognizing a linear epitope of a?: a biotechnical tool for studies on Alzheimer's disease?

Dornieden S, Mueller-Schiffmann A, Sticht H, Jiang N, Cinar Y, Woerdehoff M, Korth C, Funke SA, Willbold D (2013)

Publication Type: Journal article

Publication year: 2013

Journal

PLoS ONE Public Library of Science

Book Volume: 8

Pages Range: e59820

Journal Issue: 3

DOI: 10.1371/journal.pone.0059820

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with devastating effects. Currently, therapeutic options are limited to symptomatic treatment. For more than a decade, research focused on immunotherapy for the causal treatment of AD. However, clinical trials with active immunization using A? encountered severe complications, for example meningoencephalitis. Consequently, attention focused on passive immunization using antibodies. As an alternative to large immunoglobulins (IgGs), A? binding single-chain variable fragments (scFvs) were used for diagnostic and therapeutic research approaches. scFvs can be expressed in E. coli and may provide improved pharmacokinetic properties like increased blood-brain barrier permeability or reduced side-effects in vivo. In this study, we constructed an scFv from an A? binding IgG, designated IC16, which binds the N-terminal region of A? (A?(1-8)). scFv-IC16 was expressed in E. coli, purified and characterized with respect to its interaction with different A? species and its influence on A? fibril formation. We were able to show that scFv-IC16 strongly influenced the aggregation behavior of A? and could be applied as an A? detection probe for plaque staining in the brains of transgenic AD model mice. The results indicate potential for therapy and diagnosis of AD.

Authors with CRIS profile

Heinrich Sticht Professur für Bioinformatik

Involved external institutions

Forschungszentrum Jülich / Research Centre Jülich (FZJ) DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE)

How to cite

APA:

Dornieden, S., Mueller-Schiffmann, A., Sticht, H., Jiang, N., Cinar, Y., Woerdehoff, M.,... Willbold, D. (2013). Characterization of a single-chain variable fragment recognizing a linear epitope of a?: a biotechnical tool for studies on Alzheimer's disease? PLoS ONE, 8(3), e59820. https://doi.org/10.1371/journal.pone.0059820

MLA:

Dornieden, Silke, et al. "Characterization of a single-chain variable fragment recognizing a linear epitope of a?: a biotechnical tool for studies on Alzheimer's disease?" PLoS ONE 8.3 (2013): e59820.

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