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Increased levels of DNA breaks in cerebral cortex of Alzheimer's disease patients
Open accessAbstract
It has been hypothesized that Alzheimer's disease (AD) is caused by an accumulation of damage in DNA due to defective DNA-repair (21). Attempts to test this hypothesis by determining the activity of DNA-repair systems in nonneuronal cells from AD patients and controls so far provided conflicting results. An alternative approach is the direct comparison of DNA-damage levels in neuronal tissue of AD patients and controls. In the present study we assayed the level of DNA breaks and alkali-labile sites in cerebral cortex tissue samples from AD patients and controls obtained from rapid autopsies. Our data on 11 AD patients and 8 control subjects indicate an at least two-fold higher level of DNA damage in cortex of AD patients as compared to controls.
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“A plethora of studies document increased levels of both SSBs and DSBs in AD, HD, PD, and ALS (Mullaart et al, 1990; Adamec et al, 1999; McKinnon, 2013, 2017; Madabhushi et al, 2014; Alt & Schwer, 2018; Shanbhag et al, 2019; Thadathil et al, 2021), and their accumulation seem to correlate with important milestones in disease progression.”
From Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease (2022) · cites this paper as Mullaart et al, 1990
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“In AD, a two-fold increase in DNA damage has been found in the cortex compared to healthy controls [113].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [113]
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Sultan, A. (2010) · theses.fr (ABES) · doi:10.70675/98c582c8z1d31z4edazbbfaz92750b338b46
Therapeutic targeting of DNA repair pathway dysregulation in aging, cancer, and neurodegeneration
Kumar, V., Kashif, M., Singh, V., Rawat, R. S., Khan, A., Sarkar, G. C., & Majood, M. (2026) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2026.2683686
Brainstem pathology in SIDS and in a comparative piglet model
Machaalani, R. (2003) · The Sydney eScholarship Repository (The University of Sydney)
Metadata
- Authors
- Mullaart, E., Boerrigter, M. E. T. I., Ravid, R., Swaab, D. F., & Vijg, J.
- Affiliations
- Netherlands Organisation for Applied Scientific Research (NL)
- Corresponding author
- Vijg, Jan
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1990-05
- Volume
- 11
- Issue
- 3
- Pages
- 169-173
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2072092279
- Cited by
- 201
- References
- 34
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 12 · 2022: 11 · 2021: 5 · 2020: 16 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 10 · 2013: 8 · 2012: 5
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- green
- pure.knaw.nl
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- TNO Repository (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, DNA damage, DNA strand breaks, cerebral cortex, alkali-labile sites, DNA repair, neuronal DNA damage, neuropathology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, DNA Damage, Female, Humans, Male, Middle Aged
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