New research has identified a gene that could be responsible for increasing the risk of Alzheimer’s disease in women, offering a potential explanation as to why the disease is more prevalent in women.
The study, published in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association, was conducted by researchers at the School of Public Health, Boston University School of Medicine (MED), and the University of Chicago who identified a connection between a protein-coding gene called MGMT and an increased risk of Alzheimer’s disease in women.
As part of the study, researchers conducted a genome-wide association study (GWAS) for Alzheimer’s in two independent datasets using different study approaches.
One approach analysed dementia in a large extended family of Hutterites, who are a population of central European ancestry who due to their isolated culture and small gene pool, are often studied for genetic determinants of disease. The individuals in this first approach of the study were all women with Alzheimer’s.
The second approach analysed data from a group of 10,340 women who had reduced levels of APOE ε4, a gene considered to hold a strong link to the development of Alzheimer’s in those aged over 65.
Researchers found a significant association between MGMT and the development of Alzheimer’s Disease.
Study co-senior author and professor of epidemiology and biostatistics at SPH and chief of biomedical genetics at MED, Lindsay Farrer said the research “is one of a few and perhaps the strongest associations of a genetic risk factor for Alzheimer’s that is specific to women.”
“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,” Farrer said.
Researchers further analysed MGMT and discovered the way in which cells manage gene activity without altering the DNA sequence of MGMT is associated with the development of Alzheimer’s proteins amyloid-β and tau, particularly in women.
Study co-senior author and chair of Human Genetics at the University of Chicago, Carole Ober, stressed that the study “highlighted the value of founder populations for genetic mapping studies of diseases like Alzheimer’s.”
“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,” Ober said.
The researchers claim this study demonstrates the importance of identifying genetic risk factors for Alzheimer’s Disease that are specific to one gender. Researchers hope to conduct further studies in the future to gain a greater understanding of MGMT’s role in causing a greater Alzheimer’s risk in women.
According to Dementia Australia, “Alzheimer’s disease is the most common form of dementia, affecting up to 70% of all people with dementia” with symptoms including frequent difficulty with memory, loss of enthusiasm in normal everyday activities, and a deterioration in social skills.
In 2022, there are an estimated 487,500 Australians living with dementia.
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