PROJECT SUMMARY (CORE A: ADMINISTRATIVE CORE) The purpose of the Administrative Core (Core A) is to ensure execution of our mission to conduct innovative, interdisciplinary research to identify and validate the molecular mechanisms contributing to tauopathy risk/protection associated with the H1/H2 haplotypes of the 17q21.31 region. The Center involves 3 geographically distributed sites in New York (Icahn School of Medicine at Mount Sinai), Los Angeles (UCLA) and San Francisco (UCSF). Interactions will occur at two levels: scientific (exchange of information and data, sharing of resources and specialized personnel) and administrative (organization of meetings and interactions within and outside the CWOW). The primary goal of Core A is to connect these physically separate sites by serving as a hub to facilitate interaction and communication between Core and Project leaders, investigators, and external scientific communities, and ensure efficient governance and oversight of the Center. This Core will ensure optimal utilization of center resources through maximization of institutional strengths and national and global opportunities to broaden knowledge about the molecular mechanisms underlying risk/protection for sporadic and familial tauopathy associated with H1/H2 haplotypes. This core is responsible for articulating the research agenda and ensuring that it is effectively accomplished. Core A will accomplish this through a structure that includes an Executive Steering Committee (ESC) led by the Director (Dr. Alison Goate) and the two associate directors (Drs. Geschwind and Kampmann) as well as Core leaders. The ESC will insure that the CWOW, national and international FTD resources are leveraged to the advantage of the CWOW and those of the wider FTD community. An External Advisory Committee will provide guidance and review to the CWOW leadership and communicate with NINDS Program Staff. The leadership will assure that the Center is aware of national and international commitments as well as of opportunities to maximize our effectiveness. In this capacity specific responsibilities include financial, administrative and regulatory management. This Core will also oversee the growth of early stage investigators within the center. We propose two topically related Projects supported by three Research Cores that leverage cutting-edge proteomic and transcriptomic approaches in brain tissue and induced pluripotent stem cell derived neurons and glia to determine the mechanisms contributing to tauopathy risk/protection associated with the H1/H2 haplotypes of the 17q21.31 region. The Data Core (Core D) will serve as a hub for integrating all data produced by Projects and Cores to be shared within and outside the CWOW. Core A will organize regular meetings to ensure progress, open communication and resources are available to serve Project and Core goals, that Projects and Cores have maximal opportunity to interact, and that Projects and Cores progress according...