Pathological accumulation of Aβ plaques throughout the hippocampus in the APP/PS1 model of AD causes critical changes in the hippocampal circuits that include degradation of dendritic spines, reductions in synapse density, decreases in synaptic AMPA receptors and increases in the intrinsic excitability of neurons [34,35,36,37]. This evidence concerns the gene PSEN1 and Alzheimer disease.