Abstract
DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer’s, Parkinson’s or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer’s disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.
Highlights
Neurodegenerative and cerebrovascular diseases represent major health problems in Western countries and are usually linked to aging
Global methylation levels were found to be significantly lower in the three pathologies in comparison to values obtained in DNA samples from healthy subjects (Figure 4)
We only found a significant correlation between age and DNA methylation in Parkinsons disease (PD) subjects. p-values obtained in the comparison of 5mC and age were close to significant in DV group
Summary
Neurodegenerative and cerebrovascular diseases represent major health problems in Western countries and are usually linked to aging. Both are complex and multifactorial disorders and are caused by a combination of genetic and environmental factors. DNA methylation is the most investigated epigenetic hallmark It is a reversible mechanism in which methyl groups are added to cytosines located in CpG (5 -Cytosine-phosphate-guanosine-3 ) nucleotides turning these cytosines into five methylcytosines (5mC). This process changes DNA stability and accessibility, regulating gene expression [8]. Hydroxymethylation is implicated in important processes such as differentiation and gene expression regulation
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