Interestingly, soluble Aβ oligomers induce EphA4 activation, whereas genetic ablation or inhibition of EphA4 prevents hippocampal LTP impairment in AD transgenic model mice [137], raising an interesting possibility that Aβ-induced enhancement in EphA4 activity may impair metaplasticity in AD by regulating AMPAR degradation. This evidence concerns the gene EPHA4 and Alzheimer disease.