Dr. LaFerla's laboratory has generated a novel triple transgenic animal model of Alzheimer's Disease (AD). This model harbors three transgenes relevant to the genetic forms of AD and develops all of the neuropathological hallmarks of the disease, including Abeta plaques, neurofibrillary tangles and synaptic deficits including deficits in LTP. In addition, these neuropathological changes in the triple trangenic mice (3xTg-AD) mimic the time course of the progression of the disease in humans. Therefore, the 3xTg-AD mice represent the best animal model of AD to date. The research proposed in this application is concerned with identifying the cognitive phenotype of the 3xTg-AD mice to determine (1) the time course of the development of any behavioral impairments on a variety of memory-related tasks and (2) whether any changes in performance on memory-related tasks correlate with the deposition of Abeta and tau.