We have also to consider that AD-associated neurodegeneration, synaptic dysfunction and cognitive decline are complex, inter-regulated and long processes where pathological and compensatory phenomenon may occur.Actually, data converge to demonstrate a complex dual role of RyR in AD acting as a potential compensatory/protective paradigm, or as a pathological hallmark amplifying the setting of histopathological lesions and synaptic deficits that are associated with the late AD stages. Here, RYR2 is linked to Mental deterioration.