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Title: Generation and therapeutic efficacy of highly oligomer-specific beta-amyloid antibodies
Authors: Hillen, Heinz ×
Barghorn, Stefan
Striebinger, Andreas
Labkovsky, Boris
Müller, Reinhold
Nimmrich, Volker
Nolte, Marc W
Perez-Cruz, Claudia
van der Auwera, Ingrid
Van Leuven, Freddy
van Gaalen, Marcel
Bespalov, Anton Y
Schoemaker, Hans
Sullivan, James P
Ebert, Ulrich #
Issue Date: Aug-2010
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:30 issue:31 pages:10369-79
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.
URI: 
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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