If Aβ oligomeric load increases further, however, excitatory neurotransmission is depressed through a range of mechanisms: internalization of synaptic N-methyl-D-aspartate receptors (NMADRs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) through calcineurin activation, activation of perisynaptic NMDARs, metabotropic glutamate receptors 5 (mGluR5s), and alpha7-nAChRs, which lead to impairment of LTP and facilitation of LTD, as well as spine loss in mouse models of AD such as Tg2576 and Swedish mutant APP (APPswe) [62,63]. This evidence concerns the gene APP and Alzheimer disease.