Reduction of beta-amyloid plaques in brain of transgenic mouse model of Alzheimer's disease by EFRH-phage immunization.
Antibodies to the epitope EFRH, representing residues 3-6 within the beta-amyloid (Abeta) sequence, were previously shown to affect the solubility and disaggregation of Abeta fibrils in vitro. Here, we describe a novel method of immunization, using as antigen the EFRH peptide displayed on the surface of the filamentous phage. The EFRH phage evoked effective auto-immune antibodies in amyloid precursor protein [V717I] (APP[V717I]) transgenic mice that recapitulate the amyloid plaques and vascular pathology of Alzheimer's disease (AD). The immunization provoked a considerable reduction in the number of Abeta amyloid plaques in the brain of the transgenic mice and may serve as the basis for anti-Abeta vaccine.
Frenkel
Dan
D
Department of Molecular Microbiology & Biotechnology, The George S Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Tel-Aviv 69978, Israel.
Dewachter
Ilse
I
Van Leuven
Fred
F
Solomon
Beka
B
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D023582:Alzheimer Vaccines / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology; D001923:Brain Chemistry; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D017912:Inovirus; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D023421:Models, Animal; D019151:Peptide Library; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000473:pathology; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D001323:Autoantibodies; D000939:Epitopes; D019151:Peptide Library; D014614:Vaccines, Synthetic