title: Characterization of a single-chain variable fragment recognizing a linear epitope of aβ: a biotechnical tool for studies on Alzheimer's disease?
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 Aβ encountered severe complications, for example meningoencephalitis. Consequently, attention focused on passive immunization using antibodies. As an alternative to large immunoglobulins (IgGs), Aβ 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 Aβ binding IgG, designated IC16, which binds the N-terminal region of Aβ (Aβ(1-8)). scFv-IC16 was expressed in E. coli, purified and characterized with respect to its interaction with different Aβ species and its influence on Aβ fibril formation. We were able to show that scFv-IC16 strongly influenced the aggregation behavior of Aβ and could be applied as an Aβ detection probe for plaque staining in the brains of transgenic AD model mice. The results indicate potential for therapy and diagnosis of AD.
authors.affiliation: Institute of Complex Systems (ICS-6), Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Dornieden
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller-Schiffmann
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sticht
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Cinar
authors.forename: Michael
authors.initials: M
authors.lastname: Wördehoff
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
authors.forename: Susanne Aileen
authors.initials: SA
authors.lastname: Funke
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism; D010539:Permeability; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D016415:Sequence Alignment; D057127:Single-Chain Antibodies / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D000939:Epitopes; D007074:Immunoglobulin G; D008024:Ligands; D057127:Single-Chain Antibodies; D013844:Thiazoles; C009462:thioflavin T
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