(300 WORDS MAX) Alzheimer's disease (AD) is a tragic neurodegenerative disorder that currently has no known cure or means to effectively delay the disease progression. While beta amyloid plaques (AƒÒ), neurofibrillary tangles, and cognitive decline are late-stage markers of AD, it is not clear what is involved in the earlier stages of AD pathogenesis. Recent studies in AD models have identified an increase in intracellular Ca2+ release (up to 8-fold!) which precedes the diagnostic histopathological and cognitive changes of AD. Under healthy conditions, these Ca2+ signals are required to maintain normal cellular functions. Consequently, sustained upregulation of neuronal Ca2+ release may have pathophysiological implications for neuronal function. Specifically for AD, upregulated intraneuronal Ca2+ may increase AƒÒ peptide aggregation and hyper-phosphorylation of tau, initiate cell death, and interfere with neuronal communications that support cognitive function. We recently have discovered that a particular Ca2+ channel underlies this effect (the ryanodine receptor), and have been able to normalize the Ca2+ dysregulation using a novel blocker of this channel. We are testing whether long-term treatment of this clinically safe compound early in the disease state can block or reduce the devastating late-stage effects of AD. This represents a novel approach in targeting early mechanisms or accelerators of the disease, rather than targeting the late-stage components of the disease.