RYR2 and Alzheimer disease: Increased RyR-evoked Ca2+ release was shown to occur within synapse-dense regions of CA1 pyramidal neurons of young 3xTg-AD mice and the double transgenic mice co-expressing mutated PS1 and βAPP (PS1M146V/APPswe) and significantly increases the amplitude of spontaneous postsynaptic potentials and the frequency of events responses in 3xTg-AD as compared to non-transgenic neurons[100,166].