MAPT and Alzheimer disease: A recent study showed chronic activation of E-NMDARs promoted amyloidogenic KPI-APP expression leading to neuronal Aβ release, representing a pathological mechanism of E-NMDARs in AD development.11 Another study suggested a toxic exposure to glutamate enhances tau mRNA expression in primary neuronal cultures.13 However, as glutamate incubation activates both the synaptic and extrasynaptic NMDA receptors, the role of E-NMDARs in this process was not distinguished.