Generation of anti-beta-amyloid antibodies via phage display technology towards Alzheimer's disease vaccination.
The pathology of Alzheimer's disease (AD) shows a significant correlation between beta-amyloid peptide (betaAP) deposition and the clinical severity of dementia. The ability of site-directed antibodies towards the N-terminal region of beta-amyloid peptide to suppress in vitro formation of toxic beta-amyloid serves as a factual basis for in vivo investigations. We localized the epitope of these anti-aggregating antibodies, and injection of phage displaying this epitope induced antibodies against the whole anti-beta-amyloid peptide. In Alzheimer's diseased transgenic mice, these antibodies are delivered from the periphery to the CNS preventing beta-amyloid formation and/or dissolving such aggregates. Performance of such antigens opens up possibilities for development of an efficient, long-lasting immunization procedure for treatment of Alzheimer's disease.
Solomon
Beka
B
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel. beka@post.tau.ac.il
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000917:Antibody Formation; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D019151:Peptide Library; D014612:Vaccines / Q000276:immunology / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D016056:Immunodominant Epitopes; D019151:Peptide Library; D014612:Vaccines