(300 WORDS MAX.)Alzheimer's disease (AD) represents a prevalent illness estimated to affect 5.3 million Americans at an annual cost of $172 billion to the country's health expenses. The figures are rising precipitously as the population ages. In spite of intense research and the approval of a number of medications, the existing therapies only address symptoms not progression of the disease and do so rather poorly. The statistics support the need for novel treatments and particularly disease modifying therapies. Casein kinase 1 (CK1) represents an interesting novel target. The CK1 family is distinct from other kinase families. Highly-selective inhibitors have been documented. We present evidence for a beneficial impact of CK1 inhibition on both amyloid-beta and tau mechanisms, the two well established disease mechanisms contributing to AD. Moreover, CK1 is intimately involved in the biochemical control over circadian rhythms. In AD there is clear evidence for sleep disturbances and agitation associated with a disruption of such rhythms. CK1 antagonists are known to provide coordination of circadian rhythms. Intra-Cellular Therapies, Inc. (ITI) has developed several series of potent and selective CK1 inhibitors that are bio-available and brain penetrating. We propose in this Phase 1 proposal to test these inhibitors in a series of well-established models of AD and to elevate one candidate for pre-clinical development.