The USC ADRC focuses on mild cognitive changes related to aging, Alzheimer disease (AD) and cerebrovascular disease (CVD) in multi-ethnic communities. The USC ADRC has three overarching goals: 1) elucidate vascular contributions to Alzheimer’s disease (AD); 2) catalyze local research in AD at USC (especially Phase I/Phase II clinical trials); and 3) contribute expertise in vascular disease and imaging to national collaborative initiatives. The USC ADRC is an integral part of the national Alzheimer Disease Center (ADC) network, working closely with the National Alzheimer Coordinating Center (NACC), Alzheimer Cooperative Studies (ADCS), the Alzheimer Disease Genetics Consortium (ADGC), and Alzheimer Disease Neuroimaging Intiative (ADNI). ADRC Organization (6 Cores) The Administrative Core (Chui & Zlokovic) is responsible for the overall scientific direction of the center and the coordination of 5 other service cores, 2 research projects, and 2 pilot projects per year. Project 1 (Zlokovic) and Project 2 (Braskie) share a complementary focus on the role of Neurovascular and Metabolic Factors on AD pathogenesis, thereby giving scientific cohesiveness to the Center as a whole. The Clinical core (Schneider), assisted by the Outreach core (Williams), will constitute and follow a new Vascular Cohort Study (n-180) to support Projects 1 and 2, and will refer well-characterized participants to clinical trials, the brain donation (autopsy) program, and other research projects. The Imaging core (Law, Toga, Thompson) offers innovations in imaging the integrity of the blood brain barrier (DCE-MRI), white matter fiber tracts (DTI-MRI), and functional connectivity (fMRI). The Neuropathology core (Miller), which characterizes and shares brain tissues and biospecimens, will provide a comprehensive panel of CSF biomarkers. The Data core (Toga) will make available on line and without embargo, the imaging, biomarker, and clinical-pathological data from ADRC participants. Vascular Cohort Study (VCS) Epidemiologic studies have observed that vascular risk factors (VRF), such as hypertension and diabetes mellitus, are linked to a 1.5 to 2-fold increased risk of incident AD. With the development of amyloid-ligands for PET imaging and CSF biomarkers for β-amyloid and p-tau, it is now possible to test in vivo whether VRF are specifically linked to AD biomarkers. In Project 1, we hypothesize that the association between hypertension and β-amyloid is mediated by arterial stiffness, as assessed by perfusion MRI. In project 2, we hypothesize that increased insulin, decreased IGF-1, and decreased cholesterol efflux capacity will correlate with CSF β-amyloid. These projects will be supported by a new longitudinal Vascular Cohort Study, designed to elucidate the temporal sequence of events, leading to, accelerating, or decelerating amyloidopathy and neuronal degeneration (tau).