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dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.creatorSilzer, Talisa
dc.creatorBarber, Robert C.
dc.creatorSun, Jie
dc.creatorPathak, Gita
dc.creatorJohnson, Leigh A.
dc.creatorO'Bryant, Sid E.
dc.creatorPhillips, Nicole
dc.identifier.citationSilzer, T., Barber, R., Sun, J., Pathak, G., Johnson, L., O'Bryant, S., & Phillips, N. (2019). Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans. PloS one, 14(3), e0213527.
dc.description.abstractMitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.
dc.description.sponsorshipThis study was supported by Institute for Aging and Alzheimer's Disease Research Seed Grant 2015-RI6137, to RB and NP; and the National Institute on Aging of the National Institutes of Health under award number R01AG054073, to SO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
dc.sourcePLoS One
dc.subject.meshAlzheimer Disease
dc.subject.meshCell-Free Nucleic Acids
dc.subject.meshCognitive Dysfunction
dc.subject.meshDNA, Mitochondrial
dc.subject.meshDiabetes Mellitus, Type 2
dc.subject.meshGenetic Loci
dc.subject.meshLeucine-Rich Repeat Serine-Threonine Protein Kinase-2
dc.subject.meshMexican Americans
dc.subject.meshMiddle Aged
dc.subject.meshPolymorphism, Single Nucleotide
dc.titleCirculating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans
dc.rights.holderCopyright © 2019 Silzer et al
dc.creator.orcid0000-0001-6857-0286 (Barber, Robert C.)
dc.creator.orcid0000-0003-0582-5266 (O'Bryant, Sid E.)
dc.creator.orcid0000-0001-7769-8417 (Johnson, Leigh A.)

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)