Alzheimer´s disease (AD) and related disorders (ADRD) disproportionally impacts Hispanics/Latinos, who exhibit higher rates, earlier onset and face unique challenges due to cultural, linguistic, socioeconomic or healthcare access problems. Moreover, there is a shortage of researchers focused on ADRD in Mexican- American (MA) Hispanics, the fastest growing minority in the US. Addressing the heterogeneity of ADRD presentation and biology, using precision medicine approaches to improve risk prediction, target prevention and treatment is likely to improve outcomes for MA and others. The proposed South Texas Alzheimer disease Center (STAC) will exploit its unique geographic location in South Texas, a region of ~5 million, underserved MA to develop infrastructure and data/biosample collections that will support researchers from multiple disciplines to conduct research to diminish the burden of AD in Hispanics. We have 6 specific aims: (1) Collecting and sharing longitudinal data from patients, controls and caregivers (2) Exploring the biological heterogeneity of preclinical and clinical dementia, through deep phenotyping with clinical, imaging, genetic, omic, CSF, blood and sensory-motor biomarkers and autopsy of all these enrollees (3) Focusing especially for Aims #1 and #2 on Hispanic/Latino individuals (4) Identifying novel predictors/ biomarkers of dementia risk and resilience, including for poorly understood clinic-pathologic subgroups such as Suspected Non-Alzheimer (amyloid negative, neurodegeneration positive) Pathology [SNAP] in Hispanics with/without diabetes, (5) To recruit, train, mentor and support a diverse research workforce, largely women and minorities, to become leaders in multidisciplinary, team-based, ADRD research, (6) Bidirectional community education and engagement, research into knowledge, attitudes and practices/preferences. The STAC will develop and share culturally sensitive deep phenotyping methods beyond the Uniform Dataset (including novel cognitive, behavioral, vascular, lifestyle factors, biomarkers), genetics and multi- dimensional omics within community- based and patient and caregiver (dyadic) cohorts. Using state of the art clinical informatics and statistical methods, these rich data should permit an exploration of the molecular heterogeneity of ADRD and uncover novel biology and drug targets, treatment approaches. Finally we will collaborate, share data/samples and expertise with other institutions in Texas and around the world, especially other ADRC Centers, the NACC, NCRAD, NIAGADS. We will achieve these aims through creation of six required Cores and one component: Administrative, Clinical, Data Management and Statistical, Neuropathology, Outreach, Recruitment and Engagement, Biomarker Cores and the Research Education Component. In addition, we propose three Optional Cores: Population Neuroscience, Imaging and Genetics and Multiomics Cores. The STAC will serve as a national resource for disruptive, transformativ...