2023-04-052023-04-052023https://hdl.handle.net/20.500.12503/32238Purpose: Alzheimer’s disease (AD) is the most prevalent form of dementia and is one of America’s leading causes of death. Age is known to be the biggest risk factor for AD, and Mexican Americans are one of the fastest-aging populations in America. Mitochondrial stress and dysfunction are key players in the progression of AD and are also known to be impacted by lifestyle and environmental exposures/stressors. Mitochondrial dysfunction can cause the release of mitochondrial DNA (mtDNA) extracellularly, which can be detected in the peripheral blood (i.e., plasma). MtDNA copy number within the cell can also serve as an indicator of overall mitochondrial health, biogenesis, and/or mitophagy. This project hopes to identify population-specific differences in mitochondrial stress and dysfunction detectable in the blood and identify any relationship between AD risk factors and cognitive impairment. This data may help to further elucidate the role that mtDNA may be playing in population-specific Alzheimer's disease pathogenesis. Methods: DNA was extracted from 200uL of participant plasma and buffy coat using the Mag-Bind® Blood & Tissue DNA HDQ 96 kit (Omega Bio-tek) according to the manufacturer’s specifications. mtDNA and nuDNA copy number was assessed through absolute quantitative PCR (qPCR), targeting the mitochondrial minor arc (MinArc), and the nuclear-encoded beta-2-microglobulin gene (B2M). Data was stratified by population and sample type and linear regressions were performed to adjust for batch effects and identify factors that may influence this phenotype of mitochondrial dysfunction. Results: Population-specific differences in factors contributing to the mtDNA phenotype were observed at the p < 0.05 level. In the Mexican American cohort, there was a significant relationship between cellular mtDNA:nuDNA ratio (quantified from buffy coat) and BMI, Clinical Dementia Rating Sum of Boxes score (CDRSum), and education. Further, there was a relationship between cell-free mtDNA copy number (quantified from participant plasma), education, and CDRSum. In the non-Hispanic white cohort, there was a significant relationship between cellular mtDNA:nuDNA ratio (from buffy coat) and both age and CDRSum. Age was associated with cell-free mtDNA in the non-Hispanic white cohort. Conclusions: Evidence supports that there are population-based differences in which factors may be predictive of this blood-based phenotype of mitochondrial dysfunction. Mexican American populations seem to be more heavily influenced by environmental factors (BMI and education) whereas the non-Hispanic white population seems to be more heavily influenced by non-environmental factors (age). There also seems to be an indication of a relationship between these indicators of mitochondrial dysfunction and AD-related cognitive impairment (when measured through the CDR sum of boxes score).enposter