Biochemical Society Transactions

676th Meeting

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

D. M. Walsh, I. Klyubin, J. V. Fadeeva, M. J. Rowan, D. J. Selkoe

Abstract

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

  • Alzheimer's disease
  • amyloid β-protein
  • long-term potentiation
  • neurotoxicity
  • oligomerization
  • Aβ, amyloid-β peptide
  • AD, Alzheimer's disease
  • APP, amyloid-β precursor protein
  • CM, conditioned medium
  • IDE, insulin-degrading enzyme
  • LTP, long-term potentiation