Assessment of ccf‐Mitochondrial DNA Damage in Cognitive Impairment via NGS: Health Disparities in Mexican Americans

Mexican Americans (MAs) are the fastest growing subpopulation in the US. As this population ages, age‐related diseases such as Alzheimer’s disease (AD) will disproportionately affect MAs. MAs have a unique AD pathogenesis signature when compared to their non‐Hispanic White (NHW) counterparts. MtDNA damage may be implicated in the elevated AD burden among MAs due to the high prevalence of common risk factors for cognitive impairment (CI) including metabolic comorbidities. Mitochondrial dysfunction, oxidative damage to guanosine (8oxoG), and 5kb deletions are well‐documented in AD. MtDNA is particularly vulnerable to damage, which can affect mitochondrial function as well as act as a damage associated molecular pattern when released into the cell‐free space (ccf‐mtDNA), stimulating inflammatory responses. We hypothesize that MAs incur mtDNA damage at an elevated rate due to increased comorbidity burden altering mitochondrial function resulting in increased levels of 8oxoG and the common 5kb deletion.