Project Summary – IADRC Overall The Indiana Alzheimer’s Disease Research Center (IADRC) was established in 1991 to bring investigators and institutional resources at the Indiana University School of Medicine (IUSM) together to address the fundamental causes and treatment of Alzheimer’s disease (AD) and related dementias (ADRD). Despite many important gains, the need for targeted research is greater than ever, with an estimated 5.8 million people in the U.S. suffering from AD/ADRD. Unfortunately, we do not yet know how to prevent AD or have an approved disease modifying intervention. Both are critical to stem the growth in dementia prevalence. The overarching goal of the IADRC going forward is to support the goal of the NAPA to prevent and effectively treat AD by 2025, through innovative research on etiology, early detection, and therapeutics. Biomarker studies indicate that processes leading to AD begin at least 20 years prior to dementia, suggesting that successful interventions must be implemented early. This presents a potential opportunity for early intervention, but the field is challenged by critical barriers decreasing the prospects of timely success. The IADRC has identified the barriers as: a) The current understanding of etiology and pathophysiology is fragmented and incomplete; b) Sensitive, specific, and cost-effective methods for early detection are not available; c) Therapeutic development is hampered by the heterogeneity and complexity of ADRD; d) Shortage of data and translational scientists; and, e) Inadequate diversity at all levels. The IADRC specific aims entail innovation to overcome these barriers and accelerate research toward prevention and effective treatment: 1) Support, enhance, and expand innovative research on ADRD targeting causes, diagnosis, treatment, and prevention; 2) Provide critical research resources and infrastructure to support existing studies and enable new innovative research, utilizing a well-characterized longitudinal clinical cohort, with prioritization of diverse populations including underrepresented groups (URG) and those in preclinical and early symptomatic phases, including subjective cognitive decline and mild cognitive impairment, which will help to advance the identification of easily accessible biomarkers for early detection; 3) Identify and prioritize novel therapeutic targets from high-throughput approaches with rapid translation to proof- of-concept studies using genetic and other enrichment strategies for better biological targeting and reduction of phenotypic and biological heterogeneity for more efficient and cost-effective clinical trials; 4) Increase the number of investigators with deep expertise in advanced data sciences to bridge cellular/molecular processes of neurodegeneration and clinical phenotypes, as well as clinical and translational researchers who can move therapeutic approaches from model systems to clinical trials; 5) Provide educational and training opportunities related...