RyR expression and RyR mediated Ca2+ responses are increased in the soma and dendritic spines of hippocampal and cortical pyramidal neurons of AD mice expressing PS1 mutations (Figure 1 and Figure 2) [9,30,127], effects which are normalized by acute or chronic treatment with dantrolene, a negative allosteric RyR modulator [50,114]. Here, RYR2 is linked to Alzheimer disease.