A number of studies indicated that neuronal calcium signaling is abnormal in Alzheimer's disease and in aging brains. In particular, calcium release via intracellular calcium channel Ryanodine receptor is enhanced in AD and in aging. These results indicate that Ryanodine receptor may constitute a target for Ad treatment. To test this hypothesis we will evaluate a number of clinically relevant Ryanodine receptor antagonists in experiemnts with cellular and animal models of AD. Our results may provide important information about clinical efficacy of Ryanodine receptor antagonists such as dantrolene and tetracaine for treating AD.