Anti-oligomeric A beta Single-chain Variable Domain Antibody Blocks A beta-induced Toxicity Against Human Neuroblastoma Cells

作者：Zameer Andleeb; Kasturirangan Srinath; Emadi Sharareh; Nimmagadda Sridevi V; Sierks Michael R^*

来源：Journal of Molecular Biology, 2008, 384(4): 917-928.

DOI：10.1016/j.jmb.2008.09.068

• phage display
• ScFv
• A beta
• Alzheimer's disease
• oligomers

The Amyloid-beta (A beta) peptide is a major component of the amyloid plaques associated with Alzheimer's disease (AD). Recent studies suggest that the most toxic forms of A beta are small, soluble oligomeric aggregates. Here, we report the isolation and characterization of a single-chain variable domain (scFv) antibody isolated against oligomeric A beta using a protocol developed our laboratory that combines phage display technology and atomic force microscopy (AFM). Starting with a randomized, single framework phage display library, after three rounds of selection against oligomeric A beta, we identified an scFv that bound oligomeric A beta specifically, but not monomeric or fibrillar forms. The anti-oligomeric scFv inhibits A beta aggregation and toxicity, and reduces the toxicity of preformed oligomeric A beta towards human neuroblastoma cells. When used to probe samples of human brain tissue, the scFv reacted with AD tissue but not a healthy control or Parkinson's disease brain samples. The anti-oligomeric A beta scFv therefore has potential therapeutic and diagnostic applications in specifically targeting or identifying the toxic morphologies of A beta in AD brains.

• 出版日期2008-12-26