Alzheimers disease involves the progressive degeneration of the brain, severely impacting mental faculties. Since the Ca hypothesis of Alzheimers was proposed in 1994, several studies have shown that disruptions in Ca signaling are the primary cause of Alzheimers disease. Familial Alzheimers disease has been strongly linked to mutations in the presenilin 1 (PS1), presenilin 2 (PS2), and amyloid precursor protein (APP) genes. All of the mutated forms of these genes observed to date have been found to cause abnormal Ca signaling in the ER. Mutations in PS1 have been shown to increase IP-mediated Ca release from the ER in several animal models. Calcium channel blockers have been used to treat Alzheimer's disease with some success, and the use of  lithium to decrease IP turnover has also been suggested as a possible method of treatment.