The increased levels of glutamate and of Aβ oligomers, occurring in early AD phases, affect NMDAR subunits, NR2A and NR2B, which are crucial for synaptic plasticity, being the increased NR2B levels particularly associated with LTP inhibition and metaplasticity inversion in hippocampal slices of a transgenic AD mouse model (AβPP23) with impaired spatial working memory (Balducci et al., 2010). This evidence concerns the gene GRIN2A and Alzheimer disease.