By studying DNA from more than 1.5 million people, researchers have identified points of DNA that increase the risk of cardiovascular disease and also heighten the risk for Alzheimer’s disease.
Scientists have long been aware of connections between variations of the APOE gene, which is involved in cholesterol and lipid metabolism, and Alzheimer’s disease. That gene is known to double the risk for Alzheimer’s disease in some patients and increase risk by up to 12 times in others.
But in the new study, which appears in Acta Neuropathologica, researchers identified other DNA points that also appear to be involved both in cardiovascular disease risk and the risk for Alzheimer’s.
“These findings represent an opportunity to consider repurposing drugs that target pathways involved in lipid metabolism,” says co-senior author Celeste M. Karch, assistant professor of psychiatry at Washington University School of Medicine in St. Louis.
“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. Our study emphasizes that there’s much to learn about how genes driving Alzheimer’s disease risk also increase the risk for other health problems, particularly cardiovascular disease, and vice versa. So we really need to think about these risks more holistically.”
Family history
For the study, the largest genetic study of Alzheimer’s disease, researchers looked at differences in the DNA of people with factors that contribute to heart disease or Alzheimer’s disease and identified 90 points across the genome that were associated with risk for both diseases.
The analysis confirmed that six of the 90 regions had very strong effects on Alzheimer’s and heightened blood lipid levels, including several within genes that had not previously been linked to dementia risk. These included several points within the CELF1/MTCH2/SPI1 region on chromosome 11 that research had previously linked to the immune system.
“…if you carry this handful of gene variants, you may be at risk not only for heart disease but also for Alzheimer’s.”
The researchers confirmed their most promising findings in a large genetic study of healthy adults by showing that these same risk factors were more common in people with a family history of Alzheimer’s, even though they had not themselves developed 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 elevated triglyceride and cholesterol levels (HDL, LDL, and total cholesterol)—to see if any of these well-recognized risk factors for heart disease also were genetically related to Alzheimer’s risk.
Lipid metabolism
“The genes that influenced lipid metabolism were the ones that also were related to Alzheimer’s disease risk,” Karch says. “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.”
Although more research is needed, the new findings suggest that if researchers could target the right genes and proteins, it may be possible to lower the risk for Alzheimer’s disease in some people by managing their cholesterol and triglycerides, says co-senior author Rahul S. Desikan, an assistant professor of neuroradiology at the University of California, San Francisco.
“These results imply that irrespective of what causes what, cardiovascular and Alzheimer’s pathology co-occur because they are linked genetically. That is, if you carry this handful of gene variants, you may be at risk not only for heart disease but also for Alzheimer’s.”
The National Institute on Aging at the National Institutes of Health funded the work.
