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Gene discovery may explain why more women get Alzheimer’s disease

Scientists have identified a gene that appears to increase the risk of Alzheimer’s in women, which offers new potential clues as to why more women are diagnosed with the disease than men. The gene, O6-methylguanine-DNA-methyltransferase, or MGMT, plays an important role. important role in how the body repairs DNA damage in both men and women. But researchers have found no association between MGMT and Alzheimer’s in men. “It’s a specific finding for women, perhaps one of the strongest associations of a genetic risk factor for Alzheimer’s in women,” said lead co-author of the study Lindsay Farrer, chief. of Biomedical Genetics at Boston University School of Medicine. Two-thirds of the 6.5 million Americans currently living with devastating brain disease are women, according to the Alzheimer’s Association. It is a trend that is maintained around the world. “Women, due to unique genetic risk factors such as APOE ε4 and MGMT, and sex-specific risk factors such as sudden estrogen depletion during the perimenopausal transition, may be on the fast track to the disease while men are sitting in the traffic, ”said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Schmidt College of Medicine at Florida Atlantic University, who did not participate in the study. The APOE ε4 gene is considered the strongest risk factor. for the future development of Alzheimer’s in people over 65, which is “especially true for women, who are more affected by APOE ε4 than men,” Isaacson said. However, many women with APOE ε4 do not develop Alzheimer’s, while Women without the gene may still develop the disease. “Perhaps MGMT is an important missing piece in the risk prediction puzzle for these women, but more studies are needed,” Isaacson said. A lucky discoveryThe discovery of the existence of the new gene was made in two completely separate groups of people. A team of researchers from the University of Chicago was analyzing the genetic makeup of a small group of Hutterian Brethren women living in communities in rural Montana and South Dakota. Hutterites are a closed population that marry within their own ranks and maintain extensive genealogical records, making them an excellent choice for genetic research. “The relatively uniform environment and reduced genetic variation of hutterites increases our ability to find associations in smaller sample sizes than necessary for studies in the general population,” said study co-author Carole Ober, president of human genetics at the University of Chicago, in a statement. When the new association with MGMT appeared in his analysis, Ober contacted Farrer of Boston to see if he could help replicate his findings. Farrer, who was in the midst of a huge genetic analysis of more than 10,000 women from the Alzheimer’s Disease Genetics Consortium. “I told him we found exactly the same gene in our analysis,” Farrer said. “Two different studies started independently of each other happen to find the same gene, which adds a lot of confidence to me that the discovery is robust.” The combined study was published Thursday in Alzheimer’s Disease & Dementia: The Journal of the Alzheimer’s Association. Video below: Vaccine to treat Alzheimer’s in human trials in BostonA risk factor for women without APOE ε4The research team compared the findings with autopsy-tested male brain tissue and found no association between the MGMT gene and Alzheimer’s in men. When they examined MGMT through epigenetics, which is what happens when a gene is turned on or off by environmental behaviors and factors, the researchers found that its expression in women was significantly associated with the development of beta amyloid and tau, two proteins that are characteristic of Alzheimer’s disease. The association between MGMT and Amyloid plaques and tau plots was “more pronounced in women who do not have APOE ε4,” Farrer said. Considered an essential protein, a major function of APOE is to “move cholesterol in your body, and without it, you would be in trouble,” Farrer said. However, studies have found that variation in APOE ε4 can result in more fatty acid buildup than other members of the APOE family, so scientists believe there is a cholesterol pathway for Alzheimer’s. In fact, a study by Farrer that was published in March found that having high cholesterol and blood sugar in 30 years can increase your risk of developing Alzheimer’s disease decades later in life. and APOE ε4 is part of that, “Farrer said.” And there’s the inflammatory pathway, which is common to all chronic diseases. With MGMT, we may be looking for an additional pathway related in some way to DNA repair, or maybe MGMT is involved in one of these other pathways and no one knows yet how, “Farrer added. Personalized Medicine Women should work with their doctors to try to identify The interventions could include keeping blood pressure, cholesterol and blood sugar in healthy ranges, while “considering hormone replacement therapy when indicated, and advocating a healthy lifestyle for the brain, including regular exercise, Mediterranean diet, proper sleep and stress reduction techniques. “Isaacson said. At some point soon, scientists will be able to offer more personalized medicine to women, said Dr. Kellyann Niotis, a neurologist at the Weill Cornell Medicine and New York-Presbyterian Alzheimer’s, who did not participate in the study. “We will soon be able to offer women es at risk more advanced assessments, such as comprehensive genetic testing in a clinic, to more adequately assess your risk and develop customized risk reduction plans for optimal brain protection, ”Niotis said.

Scientists have identified a gene that appears to increase the risk of developing Alzheimer’s in women, providing new potential clues as to why more women are diagnosed with the disease than men.

The gene, O6-Methylguanine-DNA-methyltransferase, or MGMT, plays an important role in how the body repairs DNA damage in both men and women. But researchers have found no association between MGMT and Alzheimer’s in men.

“It’s a specific finding for women, perhaps one of the strongest associations of a genetic risk factor for Alzheimer’s in women,” said study lead co-author Lindsay Farrer, head of biomedical genetics at Boston University School of Medicine.

Two-thirds of the 6.5 million Americans currently living with devastating brain disease are women. according to the Alzheimer’s Association. It is a trend that is maintained around the world.

“Women, due to unique genetic risk factors such as APOE ε4 and MGMT, and sex-specific risk factors such as sudden estrogen reduction during the perimenopausal transition, may be on the fast track to disease while men are sitting. traffic, ”said Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic at Schmidt College of Medicine at Florida Atlantic University, who did not participate in the study.

The APOE ε4 gene is considered the strongest risk factor for future development of Alzheimer’s in people over 65, which is “especially true for women, who are more affected by APOE ε4 than men,” Isaacson said.

However, many women with APOE ε4 they do not develop Alzheimer’s, while women without the gene can still develop the disease.

“MGMT may be an important missing piece in the risk prediction puzzle for these women, but more studies are needed,” Isaacson said.

A fortunate discovery

The discovery of the existence of the new gene was made in two completely separate groups of people. A team of researchers from the University of Chicago was analyzing the genetic makeup of a small group of Hutterian Brethren women living in communities in rural Montana and South Dakota. Hutterites are a closed population that marry within their own ranks and maintain extensive genealogical records, making them an excellent choice for genetic research.

“The relatively uniform environment and reduced genetic variation of hutterites increases our ability to find associations in sample sizes smaller than those needed for studies in the general population,” said study co-author Carole Ober, president of human genetics at University of Chicago. in a statement.

When the new partnership with MGMT appeared in his analysis, Ober contacted Farrer of Boston to see if he could help replicate his findings.

Farrer, who was in the midst of a huge genetic analysis of more than 10,000 women Alzheimer’s Disease Genetics Consortium study, was surprised by the call.

“I told him we found exactly the same gene in our analysis,” Farrer said. “Two different studies started independently of each other happen to find the same gene, which adds a lot of confidence to me that the finding is robust.”

The combined study was published Thursday in Alzheimer’s disease and dementia: The Journal of the Alzheimer’s Association.

Video below: Vaccine to treat Alzheimer’s in human trials in Boston

A risk factor for women without APOE ε4

The research team compared the results with autopsied male brain tissue and found no association between the MGMT gene and Alzheimer’s disease in men.

When they examined MGMT through epigenetics, which is what happens when a gene is turned on or off by environmental behaviors and factors, the researchers found that its expression in women was significantly associated with the development of beta amyloid and tau, two proteins that they are characteristic of Alzheimer’s. disease.

The association between MGMT and amyloid plaques and tau tangles was “most pronounced in women who do not have APOE ε4,” Farrer said.

Considered an essential protein, a major function of APOE is to “move cholesterol in your body, and without it, you would be in trouble,” Farrer said. However, studies found that variation in APOE ε4 can produce more fatty acid accumulation than other members of the APOE family, which led scientists to believe that there is a cholesterol pathway to Alzheimer’s.

In fact, a study by Farrer that was published in March proved that it had high cholesterol and blood sugar in your 30s may increase your risk of developing Alzheimer’s disease decades later in life.

“There are many pathways for Alzheimer’s disease. There is the lipid pathway, or cholesterol, which is now fairly well established in Alzheimer’s disease. and APOE ε4 is part of that, ”Farrer said.

“And there’s the inflammatory pathway, which is common to all chronic diseases. With MGMT, we may be looking for an additional pathway related in some way to DNA repair, or maybe MGMT is involved in some of these other pathways and no one knows yet how,” Farrer . added.

Personalized medicine

Women should work with their doctors to try to identify which path they may be on, experts advise.

Interventions could include maintaining blood pressure, cholesterol and blood sugar at healthy intervals, while “considering hormone replacement therapy when indicated, and advocating for a healthy lifestyle for the brain, including regular exercise, a diet Mediterranean-style, adequate sleep and stress reduction techniques “. Isaacson said.

At some point soon, scientists will be able to offer more personalized medicine to women, said Dr. Kellyann Niotis, a neurologist at the Weill Cornell Medicine and New York-Presbyterian Alzheimer’s Prevention Clinic who did not participate in the study.

“We will soon be able to offer women at risk more advanced assessments, such as comprehensive genetic testing in a clinic, to more adequately assess their risk and develop customized risk reduction plans for optimal brain protection,” Niotis said.

Gene discovery may explain why more women get Alzheimer’s disease Source link Gene discovery may explain why more women get Alzheimer’s disease

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