Aging / Alzheimer's
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30429
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Browsing Aging / Alzheimer's by Author "Barber, Robert C."
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Item Characterization of Mitochondrial DNA Damage in Complex Disease Using Two Different NGS Platforms(2021) Reid, Danielle; Phillips, Nicole; Barber, Robert C.; Blessing, Alexandra M.Purpose: The Hispanic/Latinx aging (65+) population is expected to increase through 2060 causing the number of Alzheimer's Disease (AD) cases in the Hispanic/Latinx population to quadruple. Several risk factors for developing cognitive impairment are prevalent among Mexican Americans (MAs), although the etiology of these associations remains unclear. Age-associated decline in mitochondrial function results in accumulation of reactive oxygen species (ROS) capable of damaging essential biomolecules, including DNA. The mitochondrial genome is particularly vulnerable to DNA damage, which has a strong correlation with AD pathology. Developing an improved method to assess mitochondrial oxidative damage may help resolve the potential association between abnormal mitochondrial function as indicated by oxidative DNA damage in cognitively impaired MAs. Oxidative damage to guanine (G) forming 8oxoG, is one of the most prevalent DNA lesions. Current methods for detection are limited and lack reproducibility. Lifestyle and/or metabolic health may contribute directly to age-related neurodegeneration. Methods: We aim to investigate the mutational load indicative of oxidative DNA damage in MAs compared to non-Hispanic white (NHW) participants in a human AD cohort, TARCC, who were diagnosed with AD, type-2 diabetes (T2D), and comorbidity (AD/T2D) using Illumina-based NGS. Additionally, we propose nanopore sequencing technology as an improved alternative to current detection/quantification methods. Results: We describe preliminary proof-of-concept results and future applications of this method to analyze mtDNA damage in participants of TARCC. Conclusion: Investigation of oxidative DNA damage may aid our understanding of the differences in manifestation of age-related dementia in MAs.Item Role of DNA Methylation in Risk for Alzheimer's Disease and Type 2 Diabetes in a Mexican American Cohort(2021) Barber, Robert C.; Abraham Daniel, Ann; Hall, Courtney; Sun, Jie; Phillips, Nicole; Silzer, TalisaPURPOSE: Age related diseases such as Alzheimer's disease (AD) and type 2 diabetes (T2D) are respectively the 6th and 7th leading cause of mortality in the US. Mexican Americans, the largest ethnic minority group in the US, have an increased likelihood of developing T2D compared to their Caucasian counterparts. With the elderly Mexican American population (≥65 years old) likely to multiply 7-fold by 2050, prevalence of AD alongside T2D is predicted to increase too. Mexican Americans have an earlier onset of AD and a metabolic heavy predisposition for AD compared to Caucasians who develop inflammation-based AD. The risk for T2D and AD is multifactorial involving epigenetic factors such as methylation, which is the addition of a methyl group to the cytosine base of DNA. We aim to establish an epigenetic association between AD and T2D unique to the Mexican American population. METHODS: Participants from the Texas Alzheimer's Research and Care Consortium (TARCC), which consists of Mexican American individuals diagnosed with either AD only, T2D only or AD and T2D matched with a Caucasian counterpart were selected. Peripheral blood was drawn from participants and individual methylation profiles collected using the Illumina Infinium MethylationEPIC chip array. Differential methylation will be assessed using the Chip Analysis Methylation Pipeline (ChAMP) package in R. RESULTS: Results obtained will be analyzed using pathway and gene set enrichment analysis tools. CONCLUSIONS: Identifying possible methylation sites associated with T2D and AD unique to the Mexican American population could contribute towards developing ethnicity-specific biomarkers and treatments.