Risk of Both Cardiovascular Disease and Alzheimer’s Linked to Same Genetic Variants, Study Suggests

Specific genes linked to an increased risk for cardiovascular disease also increase the risk for Alzheimer’s disease, according to results of a large genetic study.

Researchers also found that managing the levels of lipids in the blood, such as cholesterol and triglycerides, may reduce the risk of Alzheimer’s in certain individuals.

“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,” Rahul S. Desikan, MD, PhD, assistant professor of neuroradiology at University of California, San Francisco, and one of the study’s co-lead authors, said in a press release.

The study, “Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer’s disease,” was published in the journal Acta Neuropathologica.

Increasing epidemiological evidence suggests that cardiovascular disease and lifestyle-related risk factors affect the risk of Alzheimer’s disease.

The APOE gene, which provides instructions for the making of a protein that works as a lipid (fat) transporter and is involved in cholesterol and lipid metabolism, is the biggest genetic risk factor for Alzheimer’s disease. Genetic variations in this gene increase the risk for Alzheimer’s disease by up to 12 times in certain patients.

Researchers at the Washington University School of Medicine in St. Louis and the University of California, San Francisco performed a systematic analysis of large genome-wide association studies for Alzheimer’s disease and cardiovascular-associated risk factors.

Using data from the International Genomics of Alzheimer’s Disease Project, a group of Alzheimer’s disease cases and controls in the United States, and from the Alzheimer’s Disease Genetics Consortium, they discovered that certain regions in our DNA that are prone to small variations, known as single nucleotide polymorphisms (SNPs), may be involved in both cardiovascular and Alzheimer’s disease.

To identify whether there is an overlap between genes linking cardiovascular and Alzheimer’s disease risk, researchers analyzed DNA from more than 1.5 million people. In particular, they focused on the differences in the DNA of people with factors that contribute to heart disease — including high body mass index, type 2 diabetes, heart disease, waist hip ratio, and elevated triglyceride and cholesterol levels — or Alzheimer’s disease.

Researchers identified 90 SNPs across the genome that were associated with a risk for both diseases.

Further analysis showed that six of these SNPs, found in all groups analyzed, had very strong effects on Alzheimer’s disease and increased levels of lipids in the blood.

“The genes that influenced lipid metabolism were the ones that also were related to Alzheimer’s disease risk,” said Celeste M. Karch, PhD, assistant professor of psychiatry at Washington University School of Medicine and the study’s co-lead author. “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.”

Four of these SNPs were linked for the first time to an increased risk for Alzheimer’s disease, and three of these were confirmed in an independent group of people with a family history of Alzheimer’s.

Some SNPs were found close to three genes, namely MINK1, MBLAC1, and DDB2, which were also found to be altered in a postmortem analysis of brain tissue from Alzheimer’s patients, further supporting their potential role in the disease.

SNPs were also found within the CELF1/MTCH2/SPI1 region on chromosome 11, previously linked to the immune system.

“These results suggest several different AD [Alzheimer’s disease]-associated genetic variants within chromosome 11,” the researchers wrote.

While further research is needed to confirm the role of these SNPs in Alzheimer’s disease, these findings suggest that managing the levels of lipids in the blood, such as cholesterol and triglycerides, may lower certain people’s risk for Alzheimer’s disease.

“These findings represent an opportunity to consider repurposing drugs that target pathways involved in lipid metabolism,” Karch said. “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.”