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Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment.
J Neurochem 2006; 96(3):825-32JN

Abstract

Increasing evidence suggests that oxidative damage is associated with normal aging and several neurodegenerative diseases. Mild cognitive impairment (MCI), the phase between normal aging and early dementia, is a common problem in the elderly with many subjects going on to develop Alzheimer's disease (AD). Although increased DNA oxidation is observed in the AD brain, it is unclear when the oxidative damage begins. To determine if DNA oxidation occurs in the brain of subjects with MCI, we quantified multiple oxidized bases in nuclear and mitochondrial DNA isolated from frontal, parietal and temporal lobes and cerebellum of short post-mortem interval autopsies of eight amnestic patients with MCI and six age-matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring. We found statistically significant elevations (p < 0.05) of 8-hydroxyguanine, a widely studied biomarker of DNA damage, in MCI nuclear DNA from frontal and temporal lobe and in mitochondrial DNA from the temporal lobe compared with age-matched control subjects. Levels of 8-hydroxyadenine and 4,6-diamino-5-formamidopyrimidine were significantly elevated in nuclear DNA from all three neocortical regions in MCI. Statistically significant elevations of 4,6-diamino-5-formamidopyrimidine were also observed in mitochondrial DNA of MCI temporal, frontal and parietal lobes. These results suggest that oxidative damage to nuclear and mitochondrial DNA occurs in the earliest detectable phase of AD and may play a meaningful role in the pathogenesis of this disease.

Authors+Show Affiliations

Department of Chemistry, University of Kentucky, Lexington, KY 40536-0230, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16405502

Citation

Wang, Jianquan, et al. "Increased Oxidative Damage in Nuclear and Mitochondrial DNA in Mild Cognitive Impairment." Journal of Neurochemistry, vol. 96, no. 3, 2006, pp. 825-32.
Wang J, Markesbery WR, Lovell MA. Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. J Neurochem. 2006;96(3):825-32.
Wang, J., Markesbery, W. R., & Lovell, M. A. (2006). Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. Journal of Neurochemistry, 96(3), pp. 825-32.
Wang J, Markesbery WR, Lovell MA. Increased Oxidative Damage in Nuclear and Mitochondrial DNA in Mild Cognitive Impairment. J Neurochem. 2006;96(3):825-32. PubMed PMID: 16405502.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. AU - Wang,Jianquan, AU - Markesbery,William R, AU - Lovell,Mark A, Y1 - 2006/01/09/ PY - 2006/1/13/pubmed PY - 2006/3/31/medline PY - 2006/1/13/entrez SP - 825 EP - 32 JF - Journal of neurochemistry JO - J. Neurochem. VL - 96 IS - 3 N2 - Increasing evidence suggests that oxidative damage is associated with normal aging and several neurodegenerative diseases. Mild cognitive impairment (MCI), the phase between normal aging and early dementia, is a common problem in the elderly with many subjects going on to develop Alzheimer's disease (AD). Although increased DNA oxidation is observed in the AD brain, it is unclear when the oxidative damage begins. To determine if DNA oxidation occurs in the brain of subjects with MCI, we quantified multiple oxidized bases in nuclear and mitochondrial DNA isolated from frontal, parietal and temporal lobes and cerebellum of short post-mortem interval autopsies of eight amnestic patients with MCI and six age-matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring. We found statistically significant elevations (p < 0.05) of 8-hydroxyguanine, a widely studied biomarker of DNA damage, in MCI nuclear DNA from frontal and temporal lobe and in mitochondrial DNA from the temporal lobe compared with age-matched control subjects. Levels of 8-hydroxyadenine and 4,6-diamino-5-formamidopyrimidine were significantly elevated in nuclear DNA from all three neocortical regions in MCI. Statistically significant elevations of 4,6-diamino-5-formamidopyrimidine were also observed in mitochondrial DNA of MCI temporal, frontal and parietal lobes. These results suggest that oxidative damage to nuclear and mitochondrial DNA occurs in the earliest detectable phase of AD and may play a meaningful role in the pathogenesis of this disease. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16405502/Increased_oxidative_damage_in_nuclear_and_mitochondrial_DNA_in_mild_cognitive_impairment_ L2 - https://doi.org/10.1111/j.1471-4159.2005.03615.x DB - PRIME DP - Unbound Medicine ER -