Environmental factors

One gene may be the reason more women get Alzheimer’s

A recent study led by scientists from Boston University has identified a gene that appears to increase the risk of Alzheimer’s disease in women, providing a potential new explanation as to why more women are disproportionately diagnosed with the disease—nearly twice as likely, in fact. The Alzheimer’s Association reports that of the five million Americans with AD, around 64% are women.

The study published in the Association’s journal Alzheimer’s & Dementia revealed women who inherit the gene called “MGMT” or O-6-methylguanine-DNA methyltransferase appear to have a higher risk of Alzheimer’s, while men who also have the gene do not.

The MGMT gene functions by helping the body repair damaged DNA that can occur from aging, environmental factors like pollution, and lifestyle factors such as obesity, diabetes, hypertension, smoking, heart disease, infection and inflammation in both men and women. And women who inherit the MGMT gene seem to have a higher Alzheimer’s risk compared to men with the gene because it may not be as effective in repairing the damaged DNA.

“MGMT emerged as the only significant finding and that is a gene that had never been implicated previously in Alzheimer’s disease,” said Lindsay Farrer, PhD, senior author of the study and chief of biomedical genetics at Boston University School of Medicine. “Here we have a finding of a new gene for Alzheimer’s that’s specific to women or that appears primarily impactful in women.”

Here we have a finding of a new gene for Alzheimer’s that is specific to women or that appears primarily impactful in women.

Farrer and his colleagues looked at male brain tissue but found no association between the MGMT gene and Alzheimer’s in men. But the MGMT gene expressed in women was significantly associated with the development of beta-amyloid and tau, two proteins found in Alzheimer’s.

Why are women at higher risk for Alzheimer’s, and how does the MGMT gene play a role?

According to Bernard Schreurs, PhD, professor and neuroscience researcher at West Virginia University (who was not a part of the study), AD occurs more frequently in women than men for several reasons, including women’s longer life expectancy.

In addition, while women have some protection from AD due to the presence of estrogen, those hormones tend to decrease during menopause. Studies have shown estrogen may help protect the brain from Alzheimer’s by blocking harmful effects like amyloid-beta protein, which is often found in the brains of patients with the disease.

Another reason why women tend to be more susceptible to AD is because of the presence of the gene known as APOE4—which is actually the strongest risk factor gene for Alzheimer’s disease. While both men and women can inherit MGMT and APOE4 genes, they may not be as expressed in men as they will be in women, said Kuljit Kapur, DO, chief medical officer at Transitions Care.

“Men do have the gene as well; however, men having the gene doesn’t seem to be associated with Alzheimer’s,” Kapur said, “whereas women who have the gene, many of them have Alzheimer’s.”

However, Farrer stated more studies are needed to understand the role MGMT plays in its association with Alzheimer’s, along with sex-specific associations and why the gene is linked with a higher risk of Alzheimer’s in women compared to men.

“We don’t have a full understanding of why. That’s going to require future studies,” Farrer explained. “I can only speculate and have no evidence to support it at the present time on what distinguishes men from women and how genetic factors impact men or women.”

What does this mean for you and your loved ones?

Based on the findings, Kapur said caregivers or older adults should undergo a normal screening to determine what type of dementia is present.

“Given the early onset Alzheimer’s occurs in some individuals, we need to embrace the new knowledge of gene expression and add that into the workup, alongside normal lab workup, including checking thyroid stimulating hormone (TSH), vitamin D levels, and obtaining an MRI ,” Kapur said.

Schreurs added if a loved one is concerned about recent changes in memory, they could get screened by their primary care provider, who may be able to recommend further in-depth testing by a neurologist or neuropsychologist. From there, some form of genetic testing could be performed to look at any genes implicated in AD.

If a loved one is concerned about recent changes in memory, they could get screened by their primary care provider, who may be able to recommend further in-depth testing by a neurologist or neuropsychologist.

“There are certainly benefits to finding out if someone has AD or related dementia, but for now, there is no cure for the disease,” he said. “Such knowledge may help people plan, make arrangements for future care, do things they may have been putting off, and get early treatment (limited and not always effective).”

However, because the researchers found an association but not causation between MGMT and the risk of AD in women, there isn’t anything specific women (or people in general) should be doing or changing because of these findings.

“In regards to our particular finding, it’s informative, it may be a clue as to why women get the disease more frequently than men,” Farrer said. “But we don’t yet know what the mechanism is, and certainly at this stage, there’s nothing that a person could act upon.”

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