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Cardiovascular disease, Alzheimer genetically linked – Faculty of Medicine, University of Washington at St. Louis



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Managing cholesterol, triglycerides can reduce the risk of Alzheimer's, suggests the study

Illustration by Michael Worful

Studying DNA of more than 1.5 million people, an international team of researchers, led by the Faculty of Medicine of the University of Washington at St. Louis and the University of California, San Francisco, identified DNA points that increase the risk of cardiovascular disease and also increase the risk for Alzheimer's disease.

Scientists have been aware of the connections between the variations of the APOE Gene that is involved in the metabolism of cholesterol and lipids and in Alzheimer's disease. This gene is known to bend the risk of Alzheimer's disease in some patients and increase the risk up to 12 times in others. But in the new study, the researchers identified other DNA points that also seem to be involved both in the risk of cardiovascular disease and the risk for Alzheimer's.

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

"These discoveries represent an opportunity to consider drug replication that goes into the pathways involved in lipid metabolism," said Celeste M. Karch, MD, assistant professor of psychiatry at the Faculty of Medicine, University of Washington. "Armed with these discoveries, we can begin to think if some of these drugs can be useful to prevent or delay Alzheimer's disease." Our study emphasizes that there is much to learn about how genes that lead the risk of Alzheimer's disease also increase the risk of other health problems. , especially cardiovascular diseases and vice versa. So, we really need to think about these risks in a more holistic way. "

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

They observed the differences in DNA of people with factors that contribute to heart disease or Alzheimer's disease and identified 90 points of the genome associated with risks for both diseases. His analysis confirmed that six of the 90 regions had very strong effects on the levels of Alzheimer's blood lipid and increased, including several genes that were not previously related to the risk of dementia. These included several points within the CELF1 / MTCH2 / SPI1 region of chromosome 11 previously linked to the immune system.

The researchers confirmed their most promising results 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 did not develop dementia or other symptoms such as memory loss.

They focused on specific risk factors for heart disease, such as a high body mass index, type 2 diabetes and high triglycerides and cholesterol levels (HDL, LDL and total cholesterol) to see if any of these well-known risk factors for Heart Disease was also genetically related to the risk of Alzheimer's disease.

"The genes that influenced metabolism of lipids were those that were also related to the risk of Alzheimer's disease," said Karch. "Genes that contribute to other cardiovascular risk factors, such as the body mass index and type 2 diabetes, do not seem to contribute to the genetic risk of Alzheimer's."

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

"These results imply that regardless of what causes cardiovascular and Alzheimer's coagulation because they are genetically linked, that is, if you take this handful of genetic variants, you can risk not only heart disease, but also Alzheimer's disease," he said.

Broce I, Karch C, Desikan R e col. Dissection of the genetic relationship between cardiovascular risk factors and Alzheimer's disease. Neuropathologic Act, published online November 9, 2018.

This work was supported by the National Institute of Aging at the National Institutes of Health (NIH), the subsidy numbers NIH-AG046374 and K01 AG049152. Additional financing of a National Alzheimer Coordination Center Junior Researcher Award, a Radiological Society of Resident / Fellow of North America, a Foundation of the American Society of Neuroradiology of the Alzheimer's Grant, the Research Council of Norway, the Health Authority of the Southeast Norway, the Norwegian Health Association and the KG Jebsen Foundation.

The 1,500 doctors professors of the Faculty of Medicine of the University of Washington are also the doctors of Barnes-Jewish and St. Louis Children. The Faculty of Medicine is a leader in medical research, teaching and patient care, ranked among the top 10 medical centers of the nation by U.S. News & World Report. Through its affiliations with the Barnes-Jewish and St. Louis, the Faculty of Medicine is linked to BJC HealthCare.


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