A genetic overlap between Alzheimer’s disease and two important cardiovascular disease risk factors was found by researchers at the University of California, San Diego School of Medicine: plasma lipids or fats and high levels of inflammatory C-reactive protein (CRP). The results were based on a genome-wide association project that involved hundreds of thousands of individuals and suggest these two cardiovascular phenotypes play a role in Alzheimer’s disease risk. The study was published in the online journal Circulation and offers a new clinical approach with the potential to delay disease progression.
“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. The current work finds that specific genetic signals explain a part of these relationships. 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,” said Paul M Ridker, co-author of the study.
The team used statistics to look for overlaps in single nucleotide polymorphisms (SNPs) [fragments of DNA that vary among individuals] connected with Alzheimer’s and CRP and the three components of total cholesterol: low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG).
The team found a 50-fold enrichment in Alzheimer’s SNPs for distinct levels of association with HDL, LDL, CRP and TG, which helped to identify 55 specific sites on a gene or loci (DNA sequence or chromosome site) correlated to high risk for Alzheimer’s disease. A meta-analysis of these 55 variants was also conducted on 145,000 individuals with Alzheimer’s along with healthy controls, revealing two genome-wide significant variants on both chromosomes 4 and 10; these new identified genes – HS3ST1 and ECHDC3 – had never been associated with Alzheimer’s risk for 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. 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,” said Rahul S. Desikan, research fellow and first author of the study.
“Currently, there are no disease modifying therapies and much attention has been focused upon prevention and early diagnosis. 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,” explained Ole A. Andreassen, senior co-author.
“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. 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 Alzheimer’s disease,” Anders M. Dale, senior co-author concluded.