Skip to main content
Premium Trial:

Request an Annual Quote

Alzheimer's, Cardiovascular Disease Risk Overlap Uncovered by GWAS

NEW YORK (GenomeWeb) – Certain variants linked to risk for cardiovascular disease appear to be more common in individuals with Alzheimer's disease (AD), according to researchers from the University of California, San Francisco, Washington University, and elsewhere.

As they reported on Friday in the journal Acta Neuropathologica, the researchers brought together data for more than 1.5 million participants in past genome-wide association studies to search for potential overlap between variants involved in Alzheimer's and those contributing to cardiovascular disease, cholesterol levels, and related traits and conditions.

Their search pointed to increased AD risk in those with variants implicated in a range of heart disease-related traits or conditions, particularly variants influencing cholesterol or plasma lipid biology pathways. On the other hand, variants implicated in other cardiovascular conditions, such as weight or type 2 diabetes, did not appear to track with AD.

"These results suggest that Alzheimer's and cardiovascular disease could both be influenced by genetic defects that impair the body’s ability to processes lipids properly," first author Iris Broce-Diaz, a postdoctoral researcher in the laboratory of senior author Rahul Desikan at UCSF, said in a statement. "But they also suggest that the link between Alzheimer's and other cardiovascular risk factors are not likely due to common genetics, though they could be linked by diet or other lifestyle factors."

Although past epidemiological and clinical analyses have hinted at more frequent cases of heart disease or vascular problems in individuals with AD, the team explained, potential biological ties between these conditions remain murky.

To explore this possible relationship, the researchers assessed GWAS summary statistics from prior studies of AD, coronary artery disease, triglyceride levels, type 2 diabetes, and other traits or conditions, leading to 90 suspicious SNPs peppered across 19 chromosomes.

They saw that variants implicated in traits such as low-density lipoprotein cholesterol or blood triglyceride levels were overrepresented in AD, while those implicated in diabetes, coronary artery disease, or body mass index were not.

In particular, the team's meta-analysis of the data highlighted AD- and cardiovascular disease-associated variants in or around the MBLAC1, MINK1, SPI1, and MYBPC3 genes. Three of those associations were further shored using data for hundreds of thousands of UK Biobank participants, as well as post-mortem brain expression profiles for individuals with AD.

"[W]e know that levels of cholesterol and other lipids in the blood are highly modifiable through changes in diet or with drugs," Broce-Diaz said. "This raises the possibility that we might be able to help delay or even prevent the onset of Alzheimer’s in these patients, though we'll need more data before we can say that for sure."

Based on their findings so far, the investigators are pursuing a polygenic risk score that include variants linked to heart disease or AD, in the hopes of finding patients at risk of the neurodegenerative disease.

"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," Broce-Diaz explained.