title: Novel amyloid-beta specific scFv and VH antibody fragments from human and mouse phage display antibody libraries.
abstract: 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 (Abeta1-42) 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 Abeta1-42 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 Abeta, which makes them strong therapeutic candidates due to the fact that most of the Abeta species found in the brains of AD patients display extensive N-terminus truncations/modifications.
authors.affiliation: Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), México DF, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Medecigo
authors.forename: K
authors.initials: K
authors.lastname: Manoutcharian
authors.forename: V
authors.initials: V
authors.lastname: Vasilevko
authors.forename: T
authors.initials: T
authors.lastname: Govezensky
authors.forename: M E
authors.initials: ME
authors.lastname: Munguia
authors.forename: B
authors.initials: B
authors.lastname: Becerril
authors.forename: A
authors.initials: A
authors.lastname: Luz-Madrigal
authors.forename: L
authors.initials: L
authors.lastname: Vaca
authors.forename: D H
authors.initials: DH
authors.lastname: Cribbs
authors.forename: G
authors.initials: G
authors.lastname: Gevorkian
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017104:Bacteriophage M13 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000235:genetics; D045744:Cell Line, Tumor; D000939:Epitopes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D019151:Peptide Library; D017434:Protein Structure, Tertiary / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D010446:Peptide Fragments; D019151:Peptide Library; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; C075222:amyloid beta-protein (1-42)
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