sAβPPα Improves Hippocampal NMDA-Dependent Functional Alterations Linked to Healthy Aging

This study shows a decrease in soluble amyloid-beta protein precursor-alpha (sA beta PP alpha) levels, but no change in sA beta PP alpha, in the rat hippocampus during healthy aging, associated with the weaker expression of N-methyl-D-aspartate receptor ( NMDAR)-dependent long-term potentiation (LTP) in the CA1 area of hippocampal slices. Exogenous application of recombinant sA beta PP alpha increases NMDAR activation in aged animals and could rescue the age-related LTP deficits described. In contrast, it does not affect basal synaptic transmission or glutamate release. These results indicate that improving synaptic sA beta PP alpha availability at synapses helps in reducing the functional NMDAR-related deregulation of hippocampal networks linked to aging.