Single chain Fv antibodies against the 25-35 Abeta fragment inhibit aggregation and toxicity of Abeta42.

Abstract	Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta (Abeta) protein in the brain. Immunization studies have demonstrated that anti-Abeta antibodies reduce Abeta deposition and improve clinical symptoms seen in AD. However, conventional antibody-based therapies risk an inflammatory response that can result in meningoencephalitis and cerebral hemorrhage. Here we report on the development of human-based single chain variable domain antibody fragments (scFvs) directed against the Abeta 25-35 region as potential therapeutics for AD that do not risk an inflammatory response. The 25-35 region of Abeta represents a promising therapeutic target since it promotes aggregation and is highly toxic. Two scFvs with differing affinities for Abeta were studied, and both inhibited aggregation of Abeta42 as determined by thioflavin T binding assay and atomic force microscopy analysis and blocked Abeta-induced toxicity toward human neuroblastoma SH-SY5Y cells as determined by MTT and LDH release assays. These results provide additional evidence that scFvs against Abeta provide an attractive alternative to more conventional antibody-based therapeutics for controlling aggregation and toxicity of Abeta.
Authors	Andleeb Zameer, Philip Schulz, Min S Wang, Michael R Sierks
Journal	Biochemistry (Biochemistry) Vol. 45 Issue 38 Pg. 11532-9 (Sep 26 2006) ISSN: 0006-2960 [Print] United States
PMID	16981713 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Amyloid beta-Peptides Antibodies Immunoglobulin Variable Region Peptide Fragments amyloid beta-protein (1-42)
Topics	Amino Acid Sequence Amyloid beta-Peptides (chemistry, immunology, toxicity, ultrastructure) Antibodies (immunology) Antibody Affinity (immunology) Electrophoresis, Polyacrylamide Gel Humans Immunoglobulin Variable Region (chemistry, immunology, isolation & purification) Kinetics Microscopy, Atomic Force Molecular Sequence Data Neuroblastoma Peptide Fragments (chemistry, immunology, toxicity, ultrastructure) Protein Structure, Quaternary Sequence Alignment

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