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.
Department of Neurology, Harvard Medical School and Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
D M
DM
Walsh
I
I
Klyubin
J V
JV
Fadeeva
M J
MJ
Rowan
D J
DJ
Selkoe
D000544:Alzheimer Disease / Q000235:genetics / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity*; D016923:Cell Death; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments