A Physiological Role for Amyloid-beta Protein: Enhancement of Learning and Memory

Amyloid-beta protein (A beta) is well recognized as having a significant role in the pathogenesis of Alzheimer's disease (AD). The reason for the presence of A beta and its physiological role in non-disease states is not clear. In these studies, low doses of A beta enhanced memory retention in two memory tasks and enhanced acetylecholine production in the hippocampus in vivo. We then tested whether endogenous A beta has a role in learning and memory in young, cognitively intact mice by blocking endogenous A beta in healthy 2-month-old CD-1 mice. Blocking A beta with antibody to A beta or DFFVG (which blocks A beta binding) or decreasing A beta expression with antisense directed at the A beta precursor, A beta PP, all resulted in impaired learning in T-maze foot-shock avoidance. Finally, A beta(1-42) facilitated induction and maintenance of long term potentiation in hippocampal slices, whereas antibodies to A beta inhibited hippocampal LTP. In conclusion, these results indicate that in normal healthy young animals the presence of A beta is important for learning and memory.