Aβ1–42 inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β

Amyloid-β is known to inhibit hippocampal long-term potentiation (LTP), but the underlying molecular mechanisms are only partially understood. In this capacity, Jo and colleagues report the involvement of a signaling pathway comprised of caspase-3, Akt1 and glycogen synthase kinase-3β. Amyloid-β1–42 (Aβ) is thought to be a major mediator of the cognitive deficits in Alzheimer's disease. The ability of Aβ to inhibit hippocampal long-term potentiation provides a cellular correlate of this action, but the underlying molecular mechanism is only partially understood. We found that a signaling pathway involving caspase-3, Akt1 and glycogen synthase kinase-3β is an important mediator of this effect in rats and mice.