A key limitation of our previous work and AD research in general is the predominant reliance of samples from participants of Caucasian ancestry. While metabolomics studies of AD in Caucasian cohorts have provided us with a large body of findings and leads relevant to drug discovery and development, there are currently no large- scale metabolomics studies of brain tissue available in diverse populations. This significantly hampers our ability to assess generalizability of findings across these populations or to identify pathways and molecules that are shared as well as those that may be population-specific. This is, however, of greatest importance, as contribution and types of genetic and environmental risk factors for and co-morbidities with AD may be distinct in diverse populations. For example, increased cardiovascular risk is thought to play an important role in the increased prevalence of AD in African Americans (AA) compared to whites. Given the strong metabolic underpinnings of cardiovascular and cardiometabolic health, there may be opportunities to uncover novel disease pathways and gene x environment (GxE) interactions in this population: the socioeconomic milieu is likely to be different in diverse populations compared to whites, thereby raising the possibility to discover novel metabolic changes influenced by distinct environments. To ensure success in early diagnosis, patient-stratification for clinical trials (and ultimately therapies), patient-target matching, clinical predictions based on biomarker profiling in a precision-medicine paradigm, we need to have complete knowledge on the metabolic, clinical and biomarker profiles of diverse populations, as well as Caucasians. This supplement aims to overcome this data- and knowledge-gap by generating large-scale metabolomics data using brain samples from AA and Latin American (LA) individuals, harnessing the power of multiple cohorts with ethnically diverse participants collected as part of the AMP-AD initiative. This is expected to expand the biochemical knowledge on metabolic failures in AD to include those relevant to these minority populations. By working with our AMP-AD partners, we will systematically address contributions of racial differences on metabolic aspects of brain health across the AD continuum to discover pathways and molecules linked to AD pathogenesis in these populations with elevated AD risk. Through comparing and contrasting this data to our large database of metabolomic signatures of AD in Caucasians, we aim to provide biochemical insights about mechanisms and sub-classes of disease that are common and specific to certain populations. Finally, via integrating study outcomes into our AD Atlas, we further aim to annotate AMP- AD candidate targets with respect to population relevance. All data generated through this supplement will be shared in real time with the research community through deposition in the AD Knowledge Portal. Successful completion of this project wi...