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Cardiovascular diseases, Alzheimer's genetically related – Washington School of Medicine at St. Louis



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Cholesterol management triglycerides may reduce Alzheimer's risk, studies show

Illustration by Michael Vorful

By studying DNA of more than 1.5 million people, an international team of researchers – led by the Medical Faculty in St. Louis and the University of California, San Francisco – has identified DNA points that increase the risk of cardiovascular disease and increase the risk of Alzheimer's disease.

Scientists have long been aware of the connection between variations APOE gene, which is involved in the metabolism of cholesterol and lipids and Alzheimer's disease. This gene is known to double the risk of Alzheimer's disease in some patients and increases the risk of up to 12 times in others. But in a new study, the researchers identified other DNAs that are also involved both at the risk of cardiovascular disease and at the risk of Alzheimer's disease.

The findings were published on November 12 in the journal Acta Neuropathologica.

"These findings are an opportunity to consider the reuse of drugs that target lipid metabolism pathways," said Dr. Celeste M. Karch, psychiatric assistant at the Medical School in Washington. "Armed with these findings, we can begin to think about whether some of these drugs can be useful in preventing or delaying Alzheimer's disease." Our study highlights that there is much to know about the genes that lead to Alzheimer's risk of illness also increase the risk of other health problems, especially cardiovascular disease, and vice versa. So, we really need to holistically think about these risks. "

The study is the largest genetic study of Alzheimer's disease. Karch is one of his older authors, along with Dr. Rahul S. Desikan, assistant professor, neuroradiology assistant at UC San Francisco. The first author of the study is Dr. Iris Broce-Diaz, PhD, a postdoctoral researcher at the Desikan Laboratory.

They looked at differences in DNA people with factors that contribute to heart disease or Alzheimer's disease and identified 90 points across genes that were associated with the risk of both diseases. Their analysis confirmed that six of the 90 regions had very strong effects on Alzheimer's and increased levels of lipids in the blood, including several genes that had not previously been associated with the risk of dementia. This includes several points in the box CELF1 / MTCH2 / SPI1 regions on chromosome 11 that were previously associated with the immune system.

The researchers confirmed their most likely findings in a large genetic study of healthy adults, showing that these same risk factors were more common in people with a family history of Alzheimer's disease, although they themselves did not develop dementia or other symptoms such as memory loss.

They focused on specific risk factors for heart disease – such as body mass index, type 2 diabetes, and increased levels of triglycerides and cholesterol (HDL, LDL, and total cholesterol) – to see if any of these well-recognized risk factors for the heart disease were also genetically linked to Alzheimer's risk.

"The genes that affected lipid metabolism were those who were associated with the risk of Alzheimer's disease," Karch said. "Genes that contribute to other cardiovascular risk factors, such as Body Mass Index and Type 2 Diabetes, did not contribute to the genetic risk for Alzheimer's disease."

And Desikan said that although more research is needed, new findings suggest that if true target genes and proteins can be targeted, it is possible to reduce the risk of Alzheimer's disease in some people by managing their cholesterol and triglycerides.

"These results suggest that whatever the cause, cardiovascular and Alzheimer's pathology appear because they are genetically linked, that is, if you carry this gene variant of the genes, you may be at risk not only of heart disease, but also because of Alzheimer's disease, "he said.

Broce I, Karch C, Desikan R, et al. Distribution of the genetic relationship between cardiovascular risk factors and Alzheimer's disease. Acta Neuropathologica, published on the Internet on November 9, 2018.

This work was supported by the National Institute for Aging in National Institutes of Health (NIH), grant numbers NIH-AG046374 and K01 AG049152. Additional funds from the National Alchemist Coordinating Center, Junior Investigator Avard, Radiology Society of North America, Founder of the American Society of Neuroradiology, Alzheimer's Imaging Grant, Norwegian Research Council, Health Authority of South East Norway, Norwegian Health Association and KG Jebsen Foundation.

School of Medicine, University of Washington, 1,500 physicians are also medical staff Barnes-Jevish and St. Louis Children's Hospital. The School of Medicine is the leader in medical research, continuing and nursing patients, ranked among the top ten medical schools in the country by the US company Nevs & Worl Report. Through his relationship with Barnes-Jevish and St. Louis Child Hospital, the School of Medicine is linked to BJC HealthCare.

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