Identification of Novel gene for Alzheimer's disease in women
In a new study published this week in Alzheimer's Disease & Dementia: The Journal of the Alzheimer's Association, researchers at the University of Chicago and Boston University School of Medicine (BUSM) have identified a new gene called MGMT that increases the risk of Alzheimer's in women.
The researchers conducted a genome-wide association study (GWAS) for Alzheimer's in two independent datasets using different methods. One approach focused on dementia in a large extended family of Hutterites, a founder population of central European ancestry who settled in the mid-west region of the country. Hutterites are often studied for genetic determinants of disease because they have a relatively small gene pool due to their isolated, insular culture. In this study, the individuals with Alzheimer's were all women. The second approach, predicated on evidence suggesting a link between Alzheimer's and breast cancer, analyzed genetic data from a national group of 10,340 women who lacked APOE ε4. In both datasets, MGMT was significantly associated with developing AD.
The researchers then further evaluated MGMT using multiple types of molecular data and other AD-related traits derived from human brain tissue. After thorough analysis, they found that that epigenetically regulated gene expression (i.e., one of the ways cells control gene activity without changing the DNA sequence) of MGMT, which has a role in repairing DNA damage, is significantly associated with the development of the hallmark AD proteins, amyloid-β and tau, especially in women.
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