The overall goal of the University of Washington (UW) Alzheimer's Disease Research Center (ADRC) is to continue to support and enhance an interactive multidisciplinary center milieu that enables ongoing research projects and new research initiatives addressing the pathogenesis, pathophysiology, and treatment of Alzheimer's disease (AD) and other neurodegenerative dementing disorders. An interdisciplinary collaborative team of basic and clinical investigators, health care professionals, and administrative personnel has coalesced at the UW to support and carry out an array of productive dementia programs. Primary emphasis has been directed at projects addressing the genetics of AD and other dementing disorders: other research efforts have addressed neuroendocrinology and neurochemistry of AD and normal aging, and both pharmacologic and behavioral treatments of AD. The ADRC supports and fosters productive research within the ADRC, in the greater UW research community and nationally through direct collaborations and formal multi-center programs such as the National Alzheimer's Coordinating Center (NACC), the Alzheimer's Disease Cooperative Study (ADCS), the newly integrated UW ADRC/Oregon Health and Science University ADC Neuropathology Core, and the multisite NIA genetics of late-onset familial AD initiative. The ADRC has created a career development environment in which fellows and junior faculty acquire research and clinical skills and experience working in an interdisciplinary AD research setting. Accomplishments of the previous funding period have covered a broad spectrum of basic, clinical and behavioral contributions to knowledge about AD. The current application requests continuation of seven ADRC cores and proposes three research projects. Two projects continue our productive programmatic theme of the genetics of AD: the first uses quantitative trait linkage analysis to find susceptibility genes for late onset AD;the second will identify modifiers of age of onset of presenilin-2 mutation caused AD. The third project will utilize the UW ADRC CSF and brain banks and apply proteomics to address the need for biomarkers for dementia diagnosis and monitoring disease progression.