Nucleic acid oxidation: an early feature of Alzheimer's disease

被引：97

作者：

Bradley-Whitman, Melissa A. ^{[1
,2
]}

Timmons, Michael D. ^{[3
]}

Beckett, Tina L. ^{[1
,2
]}

Murphy, Michael P. ^{[1
,2
,4
]}

Lynn, Bert C. ^{[1
,2
,3
,5
]}

Lovell, Mark A. ^{[1
,2
,3
]}

机构：

[1] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA

[2] Univ Kentucky, Alzheimers Dis Ctr, Lexington, KY 40536 USA

[3] Univ Kentucky, Dept Chem, Lexington, KY 40536 USA

[4] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA

[5] Univ Kentucky, Mass Spectrometry Facil, Lexington, KY 40536 USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2014年 / 128卷 / 02期

关键词：

Alzheimer's disease; mild cognitive impairment; mitochondrial DNA; neurodegenerative diseases; nuclear DNA; preclinical Alzheimer's disease; MILD COGNITIVE IMPAIRMENT; CEREBRAL GLUCOSE-METABOLISM; FRONTOTEMPORAL LOBAR DEGENERATION; CHROMATOGRAPHY-MASS-SPECTROMETRY; MITOCHONDRIAL-DNA; LEWY BODIES; NEUROPATHOLOGIC ASSESSMENT; ASSOCIATION GUIDELINES; AMYLOID DEPOSITION; NATIONAL INSTITUTE;

D O I：

10.1111/jnc.12444

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Studies of oxidative damage during the progression of Alzheimer's disease (AD) suggest its central role in disease pathogenesis. To investigate levels of nucleic acid oxidation in both early and late stages of AD, levels of multiple base adducts were quantified in nuclear and mitochondrial DNA from the superior and middle temporal gyri (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of age-matched normal control subjects, subjects with mild cognitive impairment, preclinical AD, late-stage AD, and non-AD neurological disorders (diseased control; DC) using gas chromatography/mass spectrometry. Median levels of multiple DNA adducts in nuclear and mitochondrial DNA were significantly (p <= 0.05) elevated in the SMTG, IPL, and CER in multiple stages of AD and in DC subjects. Elevated levels of fapyguanine and fapyadenine in mitochondrial DNA suggest a hypoxic environment early in the progression of AD and in DC subjects. Overall, these data suggest that oxidative damage is an early event not only in the pathogenesis of AD but is also present in neurodegenerative diseases in general.

引用

页码：294 / 304

页数：11

共 83 条

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