Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition.

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.