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

Biochem Soc Trans. 2002 Aug;30(4):552-7. doi: 10.1042/bst0300552.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / toxicity*
  • Cell Death
  • Humans
  • Neurons / drug effects
  • Neurons / pathology
  • Neurotoxins / chemistry*
  • Neurotoxins / toxicity
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / toxicity*


  • Amyloid beta-Peptides
  • Neurotoxins
  • Peptide Fragments