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| 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 |
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| Article Title: | Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies. |
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| Reference ID: | 1020946 |
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| 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. |
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| Affiliations: | Neuroscience Research, Global Pharmaceutical Research and Development, Abbott, D-67061 Ludwigshafen, Germany. heinz.hillen@abbott.com |
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| Date: | 2010 |
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| Reference Type: | Literature |
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| PubMed ID: | 20685980 |
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| Journal: | J Neurosci |
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| Journal Volume: | 30 |
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| Article Pages: | 10369-79 |
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| Journal ISSN: | 1529-2401 |
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| Article Chemical List: | Amyloid beta-Peptides;Amyloid beta-Protein Precursor;Antibodies, Monoclonal |
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| 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) |
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| Curation Last Updated: | 2013-05-28 22:19:48 |
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