Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized by loss of memory and cognitive capacity. Given the limitations to analyze brain cells, it is important to study whether peripheral lymphocytes can provide biological markers for AD, an interesting approach, once they represent the overall condition of the organism. To that extent, we sought to find whether lymphocytes of AD patients present DNA damage and repair kinetics different from those found in elderly matched controls (EC group) under in vitro treatment with hydrogen peroxide. We found that AD patient cells indeed showed an altered DNA repair kinetics (comet assay). Real-time quantitative analysis of genes associated with DNA stress response also showed that FANCG and CDKN1A are upregulated in AD, while MTH1 is downregulated, compared with the control group. In contrast, the expression of ATM, ATR and FEN1 genes does not seem to differ between these groups. Interestingly, TP53 protein expression was increased in AD patients. Therefore, we found that kinetics of the stress response in the DNA were significantly different in AD patients, supporting the hypothesis that repair pathways may be compromised in AD and that peripheral lymphocytes can reveal this condition.
Highlights
Alzheimer’s disease (AD) is a progressive and neurodegenerative brain disorder, characterized by the loss of memory and cognitive capacity, being severe enough to interfere with daily function and quality of life [1]
The present study assessed hydrogen peroxide-induced DNA damage, as well as the repair kinetics in lymphocytes of individuals affected by AD, compared with the elderly control (EC) group, by using the alkaline comet assay, both the conventional method and the modified version with the hOGG1 enzyme treatment
In terms of magnitude, the induction of DNA damage by H2O2 treatment was higher in the AD group, with a four-fold increase in tail intensity when compared to its mock-treatment counterpart, whereas in the EC group, a two-fold increase was observed (Figure 1C)
Summary
Alzheimer’s disease (AD) is a progressive and neurodegenerative brain disorder, characterized by the loss of memory and cognitive capacity, being severe enough to interfere with daily function and quality of life [1]. Oxidative stress can cause modifications in organic molecules, such as RNA, proteins and DNA that are thought to play a key role in the selective neuronal loss associated with aging and in the pathogenesis of neurodegenerative diseases, such as AD [18,19,20]. We assessed the expression levels of several genes associated with DNA repair and stress responses, such as ATM, ATR, FANCG, FEN1, CDKN1A, MTH1, SOD1 and TP53 genes, compared with age-matched control individuals. These alterations found in lymphocytes can be relevant and need to be further investigated to search for biomarkers that may characterize the disease
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