DESCRIPTION (provided by applicant): The goal of this proposal is to explore the relationship between neurofibrillary tangles and amyloid plaques, the hallmarks of Alzheimer's disease (AD) and the hippocampal response during a memory-taxing task in young (aged 45 to 60) participants who have a genetic risk for, but not yet any symptoms of AD. It is also to attempt to identify the earliest signs of the disease, and predictive factors for developing the disease. Volunteers, who have the APOE-4 allele, a known risk factor for AD, and their age-matched counterparts without APOE-4, will undergo functional magnetic resonance imaging while learning new associations, a task that previously has been shown to activate the hippocampus. These same subjects will undergo PET scans using FDDNP, a probe that attaches preferentially to amyloid plaques and neurofibrillary tangles and allows them to be imaged. The images will be "unfolded", or portrayed in a two-dimensional field, using a computer application designed for that purpose. This will allow specific activation within the hippocampus to be identified and localized. The PET images and fMRI images will then be superimposed in such a way that it will be possible to determine whether localization of amyloid plaques and neurofibrillary tangles correspond to increases in signal intensity during memory tasks as seen in AD patients.