The University of Pittsburgh ADRC is a multidisciplinary resource which oversees clinical assessment and care, stimulates dementia research, and trains health professionals in Alzheimer's disease (AD) and other dementias. Centered in the Department of Psychiatry and Western Psychiatric Institute and Clinic (WPIC), it involves clinicians and investigators from 17 departments in 8 school at the University. The ADRC, in newly renovated administrative and clinical space, will continue to address its three specific aims: to advance research in AD and other dementias, to train physicians and other professionals, and to promote understanding of AD and other dementias in the region and nationally. There are 5 cores in the ADRC: the Administrative Core oversees all ADRC functions, and provides scientific initiatives and directions for the Center. Within it the Data Management and Analysis Component maintains the ADRC database and provides biostatistical consultation. The Clinical Core performs clinical and research evaluations of patients and controls; follows this cohort longitudinally; provides social services and autopsy; and provides clinical data, subjects, and technical and scientific leadership for research. It also performs outreach to the African American community via a successful satellite clinic. The Neuropathology Core provides neuropathologic analyses of all cases, a well catalogued brain bank, and sophisticated image analysis and technical expertise for ADRC investigators. The Training and Information Core provides training in geriatrics and AD, provides outreach to minority groups and rural areas, and systematically evaluates ADRC programs. The newest core, the Neuroimaging Core, provides centralized acquisition, analysis, reporting and archiving of all MR imaging and spectroscopy on ADRC patients, and provides expert consultation in design of imaging studies in dementia. The projects proposed reflect the broad scientific strengths and resources at the University of Pittsburgh, our ability to attract outstanding researchers to the field, and important domains of inquiry in AD research. Project l examines amyloid and cytokine metabolism in AD brain and in animal models of brain injury and aging. Project 2 assesses the genetics of familial AD, and the role of apolipoprotein E as a risk gene in Caucasians and African Americans. Project 3 analyzes intra-cortical connections in primate and AD cortex to understand the pathological changes in AD and their relationship to cognitive decline. Project 4 assesses effects of new antidepressants on affect, functional outcome, and quality of life in depressed AD patients. Project 5 utilizes PET imaging to assess memory activation in AD and normal aging. Pilot studies include molecular genetics of the NMDA receptor, studies of neuronal death, effects of estrogen on the aging cholinergic system, and development of functional MRI. This proposal illustrates the continuing development of this mature ADRC, and its ability to manage and stimulate productive clinical and basic research, service and training activities.