Brain DNA methylation in key genes linked to Alzheimer’s

The methylation cycles of several genetic variants—28 in fact—are associated with the hallmark neurodegeneration involved in Alzheimer’s disease (AD). Some variants were found to be associated with amyloid load and others with taupathy, according to a study published online Nov. 3 in JAMA Neurology.

Lei Yu, Phd, from the Rush Alzheimer’s Disease Center, Rush University Medical Center in Chicago, and colleagues conducted a meta-analysis of ongoing genetic studies from the Religious Orders Study and the Rush Memory and Aging Project as well as data from 740 autopsied subjects aged 66 to about 108 to find out how DNA methylation affects patients’ propensity toward Alzheimer’s pathology.

Results of the study determined that DNA methylation in ABCA7, BIN1, HLA-DRB5, SLC24A4 and SORL1 all led to some aspect of Alzheimer’s pathological diagnosis.

“By leveraging genome-wide DNA methylation profiles and neuropathological data from 740 autopsied older persons, this is the first and largest study to our knowledge that has interrogated brain DNA methylation in AD loci for associations with multiple indexes for AD pathology,” the authors wrote.

A total of 60.4 percent of the subject population met the criteria for Alzheimer’s. The researchers analyzed the data to find out which variants were associated with two major pathological traits of Alzheimer’s, namely amyloid burden and helical filament tau tangle density. They found that RNA expression of BIN1 was linked to amyloid load and the expression of transcripts in ABCA7 and SORL1 were associated with density of tau tangles.   

“In summary, investigating the association of DNA methylation in target loci with AD pathology is a first step to better understand potential functional pathways that link epigenetic disruptions to the disease,” the researchers concluded.