APR 17, 2015 11:27 AM PDT

Alzheimer's, Risk Factors for Heart Disease, May Share Genes

WRITTEN BY: Judy O'Rourke
Scientists have discovered a genetic overlap between Alzheimer's disease and two key risk factors for cardiovascular disease: high levels of inflammatory C-reactive protein (CRP) and plasma lipids or fats.

Their discovery hinges on genome-wide association studies (GWAS) including more than 200,000 people. The findings suggest the two cardiovascular phenotypes play a role in Alzheimer's risk, and may offer an option for slowing the progression of the disease.

"For many years we have known that high levels of cholesterol and high levels of inflammation are associated with increased risks for Alzheimer's disease," says study co-author Paul M. Ridker, MD, MPH, the Eugene Braunwald Professor of Medicine, Harvard Medical School, and director of the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital.

"The current work finds that specific genetic signals explain a part of these relationships," he says." We now need to characterize the function of these genetic signals and see whether they can help us to design better trials evaluating inflammation inhibition as a possible method for Alzheimer's treatment."

The international team of scientists, led by researchers at University of California, San Diego School of Medicine, tapped summary statistics from GWAS studies. These studies help scientists recognize genes that are culprits in disease. This approach explores the genome, seeking tiny variations (single nucleotide polymorphisms [SNPs, pronounced "snips"]), which are found more often in people who have a specific disease than in those who don't.

The scientists were searching for overlap in SNPs linked with clinically diagnosed Alzheimer's disease and CRP and the three building blocks of total cholesterol (high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG)).

They found up to a 50-fold enrichment of Alzheimer's disease SNPs for different levels of association with CRP, LDL, HDL, and TG. What followed was identification of 55 loci (precise locations on a gene, DNA sequence, or chromosome) linked to increased Alzheimer's risk. The researchers then conducted a meta-analysis of these 55 variants, and found two genome-wide significant variants on chromosomes 4 and 10. The two identified genes-HS3ST1 and ECHDC3-had not been associated with Alzheimer's risk before.

"Our findings indicate that a subset of genes involved with elevated plasma lipid levels and inflammation may also increase the risk for developing [Alzheimer's disease]," says Rahul S. Desikan, MD, PhD, research fellow and radiology resident, UC San Diego School of Medicine and the study's first author. "Elevated levels of plasma lipids and inflammation can be modified with treatment, which means it could be possible to identify and therapeutically target individuals at increased risk for developing cardiovascular disease who are also at risk for developing Alzheimer's disease."

If this is the case, the findings could have powerful implications. Late-onset Alzheimer's is the most common form of dementia, impacting some 30 million people around the world-a number that's estimated to quadruple over the next 40 years. The costs to society at large (ranging from medical expenses to lost productivity) are staggering, the team says, noting the 2010 World Alzheimer Report estimated total annual costs at $606 billion.

"Currently, there are no disease modifying therapies and much attention has been focused upon prevention and early diagnosis," says Ole A. Andreassen, MD, PhD, senior co-author and professor of biological psychiatry, University of Oslo, Norway. "Delaying dementia onset by even just two years could potentially lower the worldwide prevalence of [Alzheimer's disease] by more than 22 million cases over the next four decades, resulting in significant societal savings."

Senior author Anders M. Dale, PhD, professor of neurosciences and radiology and director of the Center for Translational Imaging and Precision Medicine, UC San Diego, says further research is needed. "Careful and considerable effort will be required to further characterize the novel candidate genes detected in this study and to detect the functional variants responsible for the association of these loci with Alzheimer's risk," he says. "It will also be important to understand whether these genes, in combination with other known markers such as brain imaging, cerebrospinal fluid measurements, and APOE E4 status, can improve the prediction of disease risk in AD."

The findings are published in an article titled "Polygenic Overlap Between C-Reactive Protein, Plasma Lipids and Alzheimer's Disease," in the April 14, 2015 online issue of the journal Circulation.

[Source: UCSD]
About the Author
  • Judy O'Rourke worked as a newspaper reporter before becoming chief editor of Clinical Lab Products magazine. As a freelance writer today, she is interested in finding the story behind the latest developments in medicine and science, and in learning what lies ahead.
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