MAPT and Alzheimer disease: In 3xTg AD mouse models, activation of the Ca2+ permeable channel TRPV1 attenuated memory deficits and reduced the accumulation of Aβ and phosphorylated tau proteins.[88] It is well-established that overactivation of NMDARs is a key factor in increasing intracellular Ca2+ levels, which leads to synaptic dysfunction and neuron loss.