application): This proposal aims to establish a new ADRC at UCI which will focus on the basic cellular and molecular mechanisms of brain aging and AD, and seek to identify mechanisms of early pathogenic change and relate these mechanisms to cognitive and behavioral functions. Building upon the existing UCI Institute for Brain Aging and Dementia and continuing commitments by UCI to further develop Alzheimer's Disease (AD) research, the new ADRC will offer an opportunity to link pioneering basic research into early cellular and molecular mechanisms of AD to clinical applications, and apply clinical insights to basic research. The new ADRC will bring several themes to AD research: first and foremost is a cutting edge basic science perspective, second, a dedicated commitment to link basic and clinical studies, and third, an infrastructure to unite the ADRC and pioneer new initiatives that exploit the latest technological advances in bioinformatics. The technological initiatives, coordinated through the Data Management and Biostatistics Subcore (Administrative Core), are directed at fostering investigator-initiated research and bridging clinical and basic research. The four ADRC Projects are directed at investigating mechanisms hypothesized to contribute to early changes in AD brain that lead or contribute to AD progression. Three focus on cellular and molecular mechanisms. While there is always some debate, many investigators recognize three candidate mechanisms associated with the pathogenesis of AD: 1) beta-amyloid accumulation, 2) Inflammatory responses, and 3) Abnormalities in calcium homeostasis. Each of the projects addresses one of these candidate mechanisms. The fourth project will use statistical approaches in contemporary cognitive sciences (multinomial processing tree models) to define deficient sub-processes underlying losses in performance, particularly in early stage subjects. As its Long-term goal, the UCI-ADRC will strive to incorporate the latest in modern neuroscience and cognitive neuroscience to elucidate the nature of circuit dysfunction-mediated behavioral changes. The proposed ADRC infrastructure will support the projects and over 30 other faculty investigators in the ADRC.
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