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

Nucleic acid oxidation: an early feature of Alzheimer's disease.
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DOI:
10.1111/jnc.12444
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发表时间:
2014-01
影响因子:
4.7
通讯作者:
Lovell MA
Lovell MA
中科院分区:
医学2区
文献类型:
--
作者:
Bradley-Whitman MA;Timmons MD;Beckett TL;Murphy MP;Lynn BC;Lovell MA

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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.
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