DNA methylation mediates traffic-related PM2.5’s impact on Alzheimer’s disesase
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Scientists identified methylation of 24 regions, called CpG sites, in the DNA sequence, that interferes the effects of traffic-related particulate matter 2.5 (PM2.5) on brain structure changes in individuals with Alzheimer’s disease. DNA methylation is a biological process that adds chemical methyl groups to the DNA sequence. Some of the CpG sites locate in the genes related to inflammation in the central nervous system in the brain, called neuroinflammation. These findings also suggest that neuroinflammation may involve in the relation between long-term exposure of traffic-related PM2.5 and Alzheimer’s development.
Previous studies have shown that PM2.5 exposure associates with the nervous system disorders, such as migraine, stroke, and neurodegenerative diseases. The most common neurodegenerative diseases are Alzheimer’s and Parkinson’s disease.
A team of researchers found in their previous study that 1- or 3-year exposure of traffic-related PM2.5 associates with brain structure changes in patients with Alzheimer’s. They were also curious about what causes the effects of PM2.5 exposure on brain structure changes in Alzheimer’s, from biological perspective. To answer this question, they analysed brain tissue samples from 159 donors with Alzheimer’s or probable Alzheimer from the Emory Goizueta Alzheimer’s Disease Research Center (ADRC) brain bank at Emory Univeristy. With the samples, the researchers evaluated methylation levels of the CpG sites and Alzheimer’s-related structure changes in the brain.
To measure the traffic-related PM2.5 exposure, the researchers collected the air quality data from 2002 to 2019, and estimated the PM2.5 concentrations in the areas where the donors lived. They estimated the long-term exposure of PM2.5 by calculating the donors’ average exposure 1, 3, and 5 years before they passed away.
When methylation of CpG sites associates with both PM2.5 exposure and Alzheimer’s-related brain structure changes, the researchers concluded that those sites interfere.
They identified 24 CpG sites, and methylation on those sites interfered the effects of 1-, 3-, or 5-year exposure of traffic-related PM2.5 on Alzheimer’s development. Several sites locate in the genes that are linked to neuroinflammation. For example, one CpG site, called cg16342341, its methylation associated with 1-, 3-, or 5-year exposure of PM2.5, and with Alzheimer’s-related brain structure changes. Cg16342341 locates in the SORBS2 gene that involves in neuroinflammation and Alzheimer’s.
This is the first study showing the evidence of PM2.5 exposure associating with DNA methylation in human brain. The findings suggest that long-term PM2.5 exposure may cause neuroinflammation related to DNA methylation. This may lead to Alzheimer’s-related brain structure changes in individuals. However, the researchers also mentioned in their published paper that they did not directly measure the proinflammatory factors or related genes to show inflammation presence in the brain tissues. They should validate neuroinflammation’s involvement in future studies.
This study was published in Alzheimer’s & Dementia. Image credit: Pixabay
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