Amyloid-β oligomers:: their production, toxicity and therapeutic inhibition

Despite extensive genetic and animal modelling data that support a central role for the amyloid beta-protein (Abeta) in the genesis of Alzheimer's disease, the specific form(s) of Abeta 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 Abeta 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.