Epigenetic marks for Alzheimer's detected
Researchers have discovered changes in blood samples which are associated with Alzheimer’s disease, thanks to an international study of Finnish twins.
Conducted on disease-discordant twin pairs — one sibling who suffered from Alzheimer’s disease and one who was cognitively healthy — the study utilised the latest genome-wide methods to find out whether the twins’ blood samples had any disease-related differences in epigenetic marks which are sensitive to changes in environmental and lifestyle factors. The results were published in the journal Clinical Epigenetics.
Development of the late-onset form of Alzheimer’s disease is affected by both genetic and environmental factors, including lifestyle. Different environmental factors can alter function of the genes associated with the disease by modifying their epigenetic regulation, eg, by influencing the bond formation of methyl groups in the DNA’s regulatory regions which control function of the genes.
By measuring methylation levels in the DNA isolated from the Finnish twins’ blood samples, the researchers discovered epigenetic marks which were associated with Alzheimer’s disease in multiple different genomic regions. One of the marks appeared stronger also in the brain samples of the patients suffering from Alzheimer’s disease. The link between this mark and Alzheimer’s disease was confirmed in Swedish twin cohorts.
The researchers observed that the strength of the mark was influenced not only by the disease, but also age, gender and APOE genotype, which is known to associate with the risk of developing Alzheimer’s disease. Furthermore, the mark was stronger in those twins with Alzheimer’s disease who had been smoking.
The function of the gene where the mark is located is still not well understood. The gene product is suspected of inhibiting activity of certain brain enzymes that edit the code translated from DNA to direct the formation of proteins. In a previous study conducted on mice, it was noticed that removing this genomic region caused learning and memory problems, which are central symptoms of Alzheimer’s disease.
One of the leaders of the research group, Riikka Lund from the University of Turku, explained that even though the results offer new information about the molecular mechanisms of Alzheimer’s disease, more research is needed on whether the discovered epigenetic marks could be utilised in diagnostics.
“The challenges of utilising these marks include, for example, the variation of the DNA methylation level between individuals,” Lund said. “More research is also needed to clarify the potential impact of the marks on disease mechanisms and to identify the brain regions and cell types affected.”
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