BOSTON — A new gene discovered by scientists can increase the risk of Alzheimer’s disease in women.
Until now, the most well-known gene variant which increases Alzheimer’s risk in people over 65 has been APOE ε4 allele. Roughly 60 percent of people of European descent carry this particular gene. However, just one in four people in the general population carry APOE ε4 allele.
This gap tells scientists that there are still genetic variants causing Alzheimer’s disease which they still need to find. In the new study, a team from the University of Chicago and Boston University School of Medicine found that the gene MGMT can also raise the risk of dementia onset during old age.
In two different population samples, the researchers discovered MGMT had a strong connection to the onset of Alzheimer’s. The first genetic group involved a large extended family of Hutterites, a founding group of central European ancestry who settled in the American Midwest. Like the Amish, these individuals can trace their roots back to the early 16th century and they have a relatively small gene pool.
The second group included 10,340 women who lack the APOE ε4 gene variant. Scientists had been studying this group to see if there was a link between dementia and breast cancer.
“This is one of a few and perhaps the strongest associations of a genetic risk factor for Alzheimer’s that is specific to women,” says senior author Lindsay Farrer, PhD, chief of biomedical genetics at BUSM, in a media release. “This finding is particularly robust because it was discovered independently in two distinct populations using different approaches. While the finding in the large dataset was most pronounced in women who don’t have APOE ε4, the Hutterite sample was too small to evaluate this pattern with any certainty.”
What does MGMT do to the brain?
After finding this connection, the team examined MGMT using several types of molecular data and other Alzheimer’s-related traits gathered from human brain tissue. Results show MGMT plays a role in repairing DNA damage. However, it also displays a strong connection to the development of amyloid-β and tau proteins in women.
These are two of the telltale substances which appear in the brains of Alzheimer’s patients. These proteins can build up, creating harmful plaques that block and disrupt brain activity — leading to cognitive decline.
“This study highlighted the value of founder populations for genetic mapping studies of diseases like Alzheimer’s,” says senior author Carole Ober, PhD, Chair of Human Genetics at UChicago.
“The relatively uniform environment and reduced genetic variation in Hutterites increases our power to find associations in smaller sample sizes than required for studies in the general population. The validation of our findings in the larger dataset used by the Boston University group was enormously gratifying and ultimately led to supportive epigenetic mechanisms that connected both sets of GWAS results to the MGMT gene.”
The study is published in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association.