While some studies reported that RyR dysfunction in AD-related study models occurs independently of PS mutation or overexpression, namely in models expressing APP and overproducing Aβ [86,92,119,120,121,122], in many cases, PS mutation-mediated Ca2+ deregulation was associated with the alteration of the activity of RyRs (discussed beyond in PSs chapter). This evidence concerns the gene APP and Alzheimer disease.