Epitopes described in "Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies."

Article Authors:Heinz Hillen; Stefan Barghorn; Andreas Striebinger; Boris Labkovsky; Reinhold Müller; Volker Nimmrich; Marc W Nolte; Claudia Perez-Cruz; Ingrid van der Auwera; Fred van Leuven; Marcel van Gaalen; Anton Y Bespalov; Hans Schoemaker; James P Sullivan; Ulrich Ebert
Article Title:Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies.
Reference Detail
Reference ID:1020946
Abstract:Oligomers of the beta-amyloid (Abeta) peptide have been indicated in early neuropathologic changes in Alzheimer's disease. Here, we present a synthetic Abeta(20-42) oligomer (named globulomer) with a different conformation to monomeric and fibrillar Abeta peptide, enabling the generation of highly Abeta oligomer-specific monoclonal antibodies. The globulomer-derived antibodies specifically detect oligomeric but not monomeric or fibrillar Abeta in various Abeta preparations. The globulomer-specific antibody A-887755 was able to prevent Abeta oligomer binding and dynamin cleavage in primary hippocampal neurons and to reverse globulomer-induced reduced synaptic transmission. In amyloid precursor protein (APP) transgenic mice, vaccination with Abeta globulomer and treatment with A-887755 improved novel object recognition. The cognitive improvement is likely attributable to reversing a deficit in hippocampal synaptic spine density in APP transgenic mice as observed after treatment with A-887755. Our findings demonstrate that selective reduction of Abeta oligomers by immunotherapy is sufficient to normalize cognitive behavior and synaptic deficits in APP transgenic mice.
Affiliations:Neuroscience Research, Global Pharmaceutical Research and Development, Abbott, D-67061 Ludwigshafen, Germany. heinz.hillen@abbott.com
Reference Type:Literature
PubMed ID:20685980
Journal:J Neurosci
Journal Volume:30
Article Pages:10369-79
Journal ISSN:1529-2401
Article Chemical List:Amyloid beta-Peptides;Amyloid beta-Protein Precursor;Antibodies, Monoclonal
Article MeSH List:Alzheimer Disease(drug therapy; immunology); Amyloid beta-Peptides(immunology); Amyloid beta-Protein Precursor(genetics); Analysis of Variance; Animals; Antibodies, Monoclonal(immunology; therapeutic use); Cells, Cultured; Disease Models, Animal; Female; Hippocampus(cytology; immunology); Immunoprecipitation; Male; Mice; Mice, Transgenic; Neurons(cytology; immunology); Rats; Rats, Wistar; Recognition (Psychology)
Curation Last Updated:2014-10-03 22:13:52