Alzheimer’s disease and related dementias (ADRD) are a growing public health issue with tremendous cost and unfathomable aggregate suffering. Unless the diseases can be effectively treated or prevented, increasing prevalence in an aging population will escalate costs that the country will struggle to bear. With new diagnostics and therapies emerging, there has never been a greater need or opportunity to pursue groundbreaking ADRD research. This application for renewed funding of the UCSD Shiley-Marcos Alzheimer’s Disease Research Center (ADRC) explicitly aligns with the National Alzheimer’s Planning Act (NAPA) and builds on the Center’s 40-year legacy of dynamic research and engagement excellence. The Center’s exceptionally rich academic and community environment, and its commitment to team-science and inclusion, position it to work effectively as a member of the ADRC network toward achievement of national priorities. The Center’s theme and foci are to explore markers, mechanisms, and models to better understand the clinical and pathologic features and heterogeneity of ADRD, and to apply this new knowledge for a diverse, aging population. In particular, we aspire to bring world-class translational neurosciences to the study of heterogeneity and diversity in ADRD. We will develop and apply new markers and models, tailor community- engagement approaches to foster greater participation of diverse populations, and advance culturally sensitive practices in ADRD science relevant to Latinos – a growing demographic group in our region and in the U.S. This work includes innovative human cell model work fostered by its iPSC Core and state-of-the-art approaches in diversity science of its Latino Core that influences and spans Center activities. Integration across all Cores is bolstered by strong institutional commitment to the Center’s continued success and to cutting-edge, disruptive, transdisciplinary team-science. We propose the following overarching aims that reflect and unify our activities in research, education, engagement, and sharing and synergizing with the ADRC network. The Center will: 1) Support integrated, interactive Cores that conduct innovative, interdisciplinary, inclusive team-science research to benefit the diversity of individuals affected by ADRD; 2) Educate, train, and improve preparedness of a more diverse workforce; 3) Serve as a hub for scientific and community exchange and support, applying synergistic Core efforts to engage, inform, and empower patient, caregiver, and research communities; and, 4) Engage deeply in collaborative research across ADRCs and with other NIH-supported initiatives, with special emphasis on applying Center strengths to complement those within the ADRC network and extend its impact.