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Vaca, L; Medecigo, M; Manoutcharian, K; Vasilevko, V; Govezensky, T; Munguia, ME; Becerril, B; Luz-Madrigal, A; Cribbs, DH; Gevorkian, G (2010)

NOVEL AMYLOID-BETA SPECIFIC SCFV AND VH ANTIBODY FRAGMENTS FROM HUMAN AND MOUSE PHAGE DISPLAY ANTIBODY LIBRARIES

J NEUROIMMUNOL 223():104-114
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Anti-amyloid immunotherapy has been proposed as an appropriate therapeutic approach for Alzheimer's disease (AD). Significant efforts have been made towards the generation and assessment of antibody-based reagents capable of preventing and clearing amyloid aggregates as well as preventing their synaptotoxic effects. In this study, we selected a novel set of human anti-amyloid-beta peptide 1-42 (A beta 1-42) recombinant monoclonal antibodies in a single chain fragment variable (scFv) and a single-domain (VH) format. We demonstrated that these antibody fragments recognize in a specific manner amyloid-beta deposits in APP/Tg mouse brains, inhibit toxicity of oligomeric A beta 1-42 in neuroblastoma cell cultures in a concentration-dependent manner and reduced amyloid deposits in APP/Tg2576 mice after intracranial administration. These antibody fragments recognize epitopes in the middle/C-terminus region of A beta, which makes them strong therapeutic candidates due to the fact that most of the A beta species found in the brains of AD patients display extensive N-terminus truncations/modifications. (C) 2010 Elsevier B.V. All rights reserved.