| Autor: |
Hillen, Heinz, Barghorn, Stefan, Striebinger, Andreas, Labkovsky, Boris, Müller, Reinhold, Nimmrich, Volker, Nolte, Marc W., Perez-Cruz, Claudia, van der Auwera, Ingrid, van Leuven, Fred, van Gaalen, Marcel, Bespalov, Anton Y., Schoemaker, Hans, Sullivan, James P., Ebert, Ulrich |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 8/4/2010, Vol. 30 Issue 31, p10369-10379, 11p, 5 Diagrams, 7 Graphs |
| Abstrakt: |
Oligomers of the β-amyloid (Aβ) peptide have been indicated in early neuropathologic changes in Alzheimer's disease. Here, we present a synthetic Aβ20-42 oligomer (named globulomer) with a different conformation to monomeric and fibrillar Aβ peptide, enabling the generation of highly Aβ oligomer-specific monoclonal antibodies. The globulomer-derived antibodies specifically detect oligomeric but not monomeric or fibrillar Aβ in various Aβ preparations. The globulomer-specific antibody A-887755 was able to prevent Aβ 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 Aβ 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 Aβ oligomers by immuno-therapy is sufficient to normalize cognitive behavior and synaptic deficits in APP transgenic mice. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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