Finnish study offers new information about molecular mechanisms of Alzheimer's disease

Researchers have discovered new changes in blood samples associated with Alzheimer's disease. A new international study was conducted on disease-discordant Finnish twin pairs: one sibling suffering from Alzheimer's disease and the other being cognitively healthy. The researchers utilised the latest genome-wide methods to examine the twins' blood samples for any disease-related differences in epigenetic marks which are sensitive to changes in environmental factors. These differences between the siblings were discovered in multiple different genomic regions.

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, e.g. 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 the 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 to inhibit 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, Docent at the University of Turku, Riikka Lund explains 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 utilized in diagnostics.

The challenges of utilizing these marks include for example the variation of the DNA methylation level between individuals. More research is also needed to clarify potential impact of the marks on disease mechanisms and to identify the brain regions and cell types affected.

Riikka Lund, Docent at the University of Turku

The study was conducted in cross-disciplinary and international collaboration between the researches at University of Turku, Hospital District of Southwest Finland, University of Helsinki, Aalto University, Karolinska Institutet, Jönköping University, and University of Southern California. The research results have been published in the esteemed journal Clinical Epigenetics.

Source:
Journal reference:

Konki, M. et al. (2019) Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimer’s disease. Clinical Epigenetics. doi.org/10.1186/s13148-019-0729-7

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