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Heart Disease and Alzheimer’s Disease Share Genetic Links

January 25, 2019

A healthy heart and vascular system is tied to a healthier brain, a growing body of research shows. Now scientists have shown there may be a genetic basis for this link. They found that genetics may predispose some people to both Alzheimer’s disease and high levels of blood lipids such as cholesterol, a common feature of cardiovascular disease. The findings may open new opportunities to target drugs that may help to curb the onset of Alzheimer’s disease.

For the study, researchers at Washington University School of Medicine in St. Louis and the University of California, San Francisco, and other institutions looked at DNA from more than 1.5 million men and women. They identified 90 gene areas that were associated with an increased risk of both Alzheimer’s disease and cardiovascular disease. Six of the 90 regions had strong effects on Alzheimer’s risk and high levels of blood lipids like LDL, a form of “bad” cholesterol linked to heart attack risk.

“These findings represent an opportunity to consider repurposing drugs that target pathways involved in lipid metabolism,” said Celeste M. Karch, an assistant professor of psychiatry at Washington University. “Armed with these findings, we can begin to think about whether some of those drugs might be useful in preventing or delaying Alzheimer’s disease.” The study was published in the journal Acta Neuropathologica.

Researchers have previously identified a gene variant called APOE-E4 that is strongly linked to an increased risk of Alzheimer’s disease. While the function of the APOE gene is not clear, it might be involved in the production of various blood lipids. But many of the genes identified in this new study, other than APOE-E4, were not previously tied to dementia risk.

“The genes that influenced lipid metabolism were the ones that also were related to Alzheimer’s disease risk,” Dr. Karch said. “Genes that contribute to other cardiovascular risk factors, like body mass index and type 2 diabetes, did not seem to contribute to genetic risk for Alzheimer’s.”

The findings suggest that it may be possible to lower the risk for Alzheimer’s disease in some people by managing heart risk factors like high cholesterol and triglycerides, the authors say.

“If we can identify the subset of individuals whose cardiovascular and brain health is linked genetically, we think there’s a possibility that reducing their blood lipid levels could help reduce their risk of developing dementia later in life,” said Iris Broce-Diaz, the first author on the study and a researcher at the University of California, San Francisco. “Such treatments haven’t worked in clinical trials before, but this could be because we haven’t had a good way of selecting who is most likely to benefit based on their genetics.”

Earlier studies have found evidence that cardiovascular health is tied to brain health, including the risk for Alzheimer’s disease. Researcher have found, for example, that among mentally alert elderly men and women, those with signs of hardening of the arteries (atherosclerosis) were more likely to have signs of the brain plaques that are a hallmark of Alzheimer’s. Other studies have shown that high blood pressure is linked to thinking and memory problems in the elderly, as well as the presence of the plaques and tangles characteristic of Alzheimer’s disease.

Various factors can help to keep blood vessels supple and reduce the risk of cardiovascular disease. These include a heart-healthy diet–eating plenty of fruits and vegetables, choosing fats like olive oil in place of saturated fats like the fat found in red meat, and consuming fish rather than red meats. Regular exercise is also an important factor known to promote cardiovascular health and, by inference, brain health.

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Broce I, Karch C, Desikan R, et al. “Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease.” Acta Neuropathologica, Nov. 9, 2018.

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