PSEN1 and Alzheimer disease: Finally, in the presence of FAD-PS1/2 mutations, increased expression levels and activity of RyRs have been reported [53,54,55], suggesting a RyR-dependent Ca2+ hyperexcitability in AD that is antagonized by the channel inhibitor dantrolene (see [56] for an extensive discussion of this issue; see also [57] for the involvement of IP3Rs).