Nucleic acid oxidation: an early feature of Alzheimer's disease
Open accessAbstract
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. image Levels of oxidized nucleic acids in nDNA and mtDNA were found to be significantly elevated in mild cognitive impairment (MCI), preclinical Alzheimer's disease (PCAD), late‐stage AD (LAD), and a pooled diseased control group (DC) of frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) subjects compared to normal control (NC) subjects. Nucleic acid oxidation peaked early in disease progression and remained elevated. The study suggests nucleic acid oxidation is a general event in neurodegeneration.
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Increased DNA oxidation is observed in post mortem AD brain, MCI, and preclinical AD, and may exacerbate AD progression.
“Increased DNA oxidation was observed in post mortem AD brain [496], MCI [497], and preclinical AD [498], and may exacerbate AD progression [499, 500].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [496]
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- Authors
- Bradley‐Whitman, M. A., Timmons, M. D., Beckett, T. L., Murphy, M. P., Lynn, B. C., & Lovell, M. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Lovell, Mark A.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2013-10-21
- Volume
- 128
- Issue
- 2
- Pages
- 294-304
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC3947319
- OpenAlex
- W2155515447
- Cited by
- 112
- References
- 87
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 8 · 2018: 7 · 2017: 5 · 2016: 11 · 2015: 5 · 2014: 8
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (5P01-AG05119, P30-AG028383)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- Alzheimer's disease, nucleic acid oxidation, oxidative DNA damage, DNA adducts, mitochondrial DNA, nuclear DNA, hypoxia, mild cognitive impairment, preclinical Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, neurodegeneration, temporal lobe, cerebellum
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cell Nucleus, DNA, DNA Damage, DNA, Mitochondrial, Female, Humans, Male, Oxidation-Reduction, Case-Control Studies, DNA Adducts, Lewy Body Disease, Frontotemporal Dementia
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