Amyloid-beta oligomers: their production,toxicity and therapeutic inhibition |
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Authors: | Walsh D M Klyubin I Fadeeva J V Rowan M J Selkoe D J |
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Institution: | Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA. |
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Abstract: | Despite extensive genetic and animal modelling data that support a central role for the amyloid beta-protein (A beta) in the genesis of Alzheimer's disease, the specific form(s) of A beta which causes injury to neurons in vivo has not been identified. In the present study, we examine the importance of soluble, pre-fibrillar assemblies of A beta as mediators of neurotoxicity. Specifically, we review the role of cell-derived SDS-stable oligomers, their blocking of hippocampal long-term potentiation in vivo and the finding that this blocking can be prevented by prior treatment of oligomer-producing cells with gamma-secretase inhibitors. |
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