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Title
| - Single Chain Fv Antibodies against the 25−35 Aβ Fragment Inhibit Aggregationand Toxicity of Aβ42
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Abstract
| - Alzheimer's disease (AD) is characterized by the deposition of amyloid-β (Aβ) protein in thebrain. Immunization studies have demonstrated that anti-Aβ antibodies reduce Aβ deposition and improveclinical symptoms seen in AD. However, conventional antibody-based therapies risk an inflammatoryresponse that can result in meningoencephalitis and cerebral hemorrhage. Here we report on the developmentof human-based single chain variable domain antibody fragments (scFvs) directed against the Aβ 25−35region as potential therapeutics for AD that do not risk an inflammatory response. The 25−35 region ofAβ represents a promising therapeutic target since it promotes aggregation and is highly toxic. Two scFvswith differing affinities for Aβ were studied, and both inhibited aggregation of Aβ42 as determined bythioflavin T binding assay and atomic force microscopy analysis and blocked Aβ-induced toxicity towardhuman neuroblastoma SH-SY5Y cells as determined by MTT and LDH release assays. These resultsprovide additional evidence that scFvs against Aβ provide an attractive alternative to more conventionalantibody-based therapeutics for controlling aggregation and toxicity of Aβ.
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