8-hydroxy-2--deoxyguanosine and Dementia

To establish and validate a robust LC-MS/MS method for simultaneously measuring 8-oxoGuo, 8-oxodG, and NMN in serum and urine to evaluate the oxidative stress status.. A Waters TQ-XS triple quadrupole mass spectrometer system coupled with an Acquity UPLC Primer HSS T3 column was chosen. The clinical performance was verified according to the CLSI C62-A and EP-15 guidelines. Furthermore, matched serum and urine samples from 22 apparently healthy check-ups, 20 patients with atherosclerosis, and 18 individuals with dementia were evaluated.. The recovery for serum 8-oxoGuo, urine 8-oxoGuo, serum 8-oxodG, urine 8-oxodG, serum NMN, and urine NMN was 88.8-112.4%, 102.4-114.1%, 88.5-107.7%, 94.9-102.6%, 98.4-108.9%, and 88.5-108.6%, respectively. Based on the inter-assay results, total coefficient of variation, matrix effect, and carryover, the LC-MS/MS method was deemed robust. The limit of quantification was 0.017, 0.018, and 0.150 nmol/L for 8-oxoGuo, 8-oxodG, and NMN, respectively, which are suitable for accurate measurements in human serum and urine samples. Higher 8-oxoGuo and 8-oxodG levels and lower NMN levels, indicative of significantly higher oxidative stress status, were found in patients with dementia compared to healthy subjects.. We established and validated a robust LC-MS/MS method to simultaneously measure 8-oxoGuo, 8-oxodG, and NMN in serum and urine.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Chromatography, Liquid; Dementia; Humans; Tandem Mass Spectrometry

We previously found that there was a dementia subgroup with characteristics predominantly associated with diabetes mellitus (DM)-related metabolic abnormalities, referred to as "diabetes-related dementia (DrD)." We determined the possible role of oxidative stress in the pathophysiology of DrD.. In a 2013 study, we classified 175 patients with clinically diagnosed Alzheimer's disease (AD) and DM into four subgroups based on brain imaging. Among them, we measured endogenous plasma anti-oxidants, such as albumin, unconjugated bilirubin and uric acid, and urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in 58 patients of an AD group showing decreased regional cerebral blood flow of the parietotemporal lobe on single-photon emission computed tomography (AD+DM group), and in 35 patients of a DrD group showing neither decreased regional cerebral blood flow of the parietotemporal lobe nor cerebrovascular disease on magnetic resonance imaging, which is strongly associated with DM-related factors. A total of 31 patients with AD and without DM (AD-DM group) were enrolled as a control group.. The DrD group showed a significant decrease in plasma levels of anti-oxidants, and a significant increase in urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane levels in contrast to the AD-DM and AD+DM groups. Cognitive performance was negatively correlated with urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane levels in the DrD group.. These results strongly suggest that a decrease in anti-oxidant levels and an increase in oxidative damage might be involved in the pathophysiology and cognitive decline associated with DrD. Geriatr Gerontol Int 2016; 16: 1312-1318.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Alzheimer Disease; Biomarkers; Dementia; Deoxyguanosine; Diabetes Complications; Diabetes Mellitus; Female; Humans; Male; Oxidative Stress

DNA oxidative stress has been suggested as an important pathogenic mechanism in cognitive impairment and dementia. With baseline data collected from 2004 to 2008, the authors examined whether urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of global DNA oxidation, was associated with cognitive function in a sample of 1,003 Puerto Rican adults, aged 45-75 years, living in Boston, Massachusetts, and the surrounding area. Cognitive function was measured by using a battery of 7 tests: the Mini-Mental State Examination, word list learning, digit span, clock drawing and figure copying, Stroop, and verbal fluency tests. The primary outcome was a global cognitive score, averaging standardized scores across all cognitive tests. A higher 8-OHdG concentration was significantly associated with lower global cognitive scores, after adjustment for age, education, status of the gene for apolipoprotein E (APOE), and other covariates (P(trend) = 0.01). The difference in the global score, comparing participants in the 2 extreme 8-OHdG quartiles, was -0.11 (95% confidence interval: -0.20, -0.02), which was equivalent to accelerating cognitive aging by about 4 years, as observed in this population. Prospective studies are needed to elucidate whether elevated urinary 8-OHdG concentrations can predict the rate of cognitive decline and incident dementia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antibodies, Monoclonal; Apolipoproteins E; Cognition Disorders; Dementia; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Female; Humans; Incidence; Male; Massachusetts; Middle Aged; Neuropsychological Tests; Oxidative Stress; Prevalence; Puerto Rico; Severity of Illness Index