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Newly identified gene may be reason women have greater risk of Alzheimer's

New research may help explain why Alzheimer's disease is more prevalent in women than men. Photo by <a href="https://pixabay.com/users/guvo59-9285194/?utm_source=link-attribution&amputm_medium=referral&amputm_campaign=image&amputm_content=4083343">Gundula Vogel</a>/<a href="https://pixabay.com/?utm_source=link-attribution&amputm_medium=referral&amputm_campaign=image&amputm_content=4083343">Pixabay</a>
New research may help explain why Alzheimer's disease is more prevalent in women than men. Photo by Gundula Vogel/Pixabay

WASHINGTON, June 30 (UPI) -- New research has identified a novel gene -- a genetic risk factor -- for Alzheimer's disease that appears to be much stronger in women, furthering efforts to explain why they are at higher risk than men.

The discovery offers insight into other possible ways to slow or stop the disease progression, according to a prominent Alzheimer's researcher.

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Nationwide, an estimated 5.8 million people have Alzheimer's, a progressive, neurodegenerative illness and the most common form of dementia, according to the Centers for Disease Control and Prevention. Roughly six in 10 patients are women.

By 2060, the number of those afflicted with Alzheimer's is projected to nearly triple to 14 million people, the CDC says.

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To date, scientists have discovered some genetic variants that increase the risk for developing Alzheimer's, including what is called the APOE ε4 allele.

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Roughly 60% of people of European ancestry with Alzheimer's carry this genetic variant versus 26% of the general population -- implying that other genes contribute to Alzheimer's genetic makeup.

The new study by researchers at the University of Chicago and Boston University School of Medicine identifies a new gene, called MGMT, that increases the risk of Alzheimer's in women.

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"There are probably multiple messages here. One is that this is, if not the first, one of the very few genetic findings that implicates the contribution of a particular genetic effect [for Alzheimer's] to be strongest among women," Lindsay Farrer, chief of biomedical genetics at Boston University School of Medicine, told UPI.

Farrer is a senior author of the study, published Thursday in Alzheimer's Disease & Dementia: The Journal of the Alzheimer's Association.

Farrer said the APOE gene, discovered in 1993, has three variants, one of which confers a very high risk of developing Alzheimer's: a single copy of APOE ε4 means roughly a three-fold risk; two copies is a ten-fold risk.

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Yet, while APOE is a strong risk factor for Alzheimer's, it accounts for only one-fourth to one-third of cases, Farrer said. So researchers have spent nearly 30 years looking further for genetic causes of Alzheimer's -- and the new study was designed to search for a risk factor particular to women.

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Dr. Steven T. DeKosky, a professor of neurology at the University of Florida College of Medicine, and an Alzheimer's disease and traumatic brain injury researcher for four decades, told UPI the study is complex, but notable.

"It's clearly a very well-done study, with a discovery of a genetic variant that increases the likelihood of the development of Alzheimer's disease, especially in women, and then confirmed it with a second genetic population and a small group of people from a family with the genetic variant," DeKosky said.

"We've known for a long time that the prevalence of Alzheimer's disease is higher in women, previously thought to be because women live longer than men and now shown to be associated with genetic mechanisms as well," said DeKosky, deputy director of McKnight Brain Institute and a Fellow of the American Academy of Neurology.

"In addition to the discovery providing another insight into how the brain changes in Alzheimer's disease are controlled, it offers insight into other possible ways to slow or stop the disease progression," he said.

Farrer described the study's finding as particularly robust because it was discovered independently by researchers at different academic institutions analyzing two distinct populations using different methods.

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The University of Chicago's approach focused on dementia among the Hutterites, a group of central European ancestry who settled in the Midwest.

The insular group is studied often for genetic determinants of disease because its members have a relatively small gene pool. In this study, the couple of dozen Hutterites with Alzheimer's were all women.

Independently, Boston University scientists analyzed genetic data from a large national dataset of 10,340 women who lacked the APOE ε4 variant.

In both datasets, MGMT was significantly associated with developing Alzheimer's.

"I almost jumped out of my skin, because we had made the same finding with a completely different approach in a completely different population," Farrer said of the researchers in Boston and Chicago.

"The fact the genetic signal was much, much stronger in women clearly is supported by both studies," he said, "because we only found it in women and all of their [i.e., University of Chicago's] cases were in women."

The two groups of researchers exchanged information, "and that prompted us to work together on new research," conducting experiments to better understand the mechanisms involved and corroborate initial genetic findings, Farrer said.

The researchers further analyzed MGMT using multiple types of molecular data and other Alzheimer's-related traits derived from human brain tissue, according to the study's news release.

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They concluded that "MGMT, which has a role in repairing DNA damage, is significantly associated with the development of the hallmark Alzheimer's proteins, amyloid-β and tau, especially in women." Both may lead to plaque tangles in the brain.

Some studies suggest there might be a hormonal component to the development of Alzheimer's, Farrer said, "and here we have another factor, this MGMT."

However, he cautioned, "I don't want to overstate the findings. ... To better understand and prove it, one needs clear, functional evidence beyond our research -- studies to look at mechanisms related to this gene and see how these mechanisms play out in women versus men."

Farrer added: "We're going to attempt to get into that [exploration of mechanisms], but it's clearly an opportunity for other researchers to do likewise."

Separately, the Alzheimer's Association noted Wednesday that a House appropriations panel is proposing a $200 million increase in Alzheimer's and dementia research funding at the National Institutes of Health for the federal fiscal year starting Oct. 1.

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