According to a new study by an international team led by scientists at the University of California at San Francisco and at the University of Washington School of Medicine, genetics may increase the number of people with Alzheimer's disease and high blood lipids, such as cholesterol, a common feature of cardiovascular disease. In St. Louis.
The study analyzed data on a genome wider than 1.5 million people, making it one of the largest ever studies of Alzheimer's and genetics. The researchers hope the findings will lead to an improvement in early diagnosis and new prevention strategies for Alzheimer's patients, which currently affect 5.7 million people in the United States and have no medication.
Multiple clinical and epidemiological evidence suggested a link between heart disease and Alzheimer's disease, but the biological relationship between the two conditions remained controversial. Many patients diagnosed with Alzheimer's disease also show signs of cardiovascular disease, and postmodem studies reveal that many Alzheimer's brains show signs of vascular disease, which some scientists believe may cause dementia. These observations have led to the hope of preventing Alzheimer's by treating cardiovascular symptoms, but preliminary genetic studies and failed clinical trials of cardiovascular drugs called statins in Alzheimer's disease have questioned this possibility.
The new study, published on November 9, 2018 Acta Neuropathology, Shows that Alzheimer's disease and cardiovascular disease share common genetics in some people and raises new questions about whether this common biology can be directed to slow down or prevent both diseases.
"These results suggest that no matter what causes heart disease, but also Alzheimer's," he says, "if you carry a small number of genetic variants, you may be at risk not only for heart disease but also for Alzheimer's, A scientist, a laboratory scientist whose scientists are known to develop what is known as a "hazard risk" for Alzheimer's patients, predicting the age at which a person may begin to experience symptoms of dementia based on their genetic background.
To identify genetic variants that risk cardiovascular disease and Alzheimer's disease, the researchers used statistical techniques tested by Desikan's laboratory with Ole Andreasen, MD, PhD, at the University of Oslo and Anders Dale, PhD, at the University of California, San Diego, which allowed them to combine multiple Of large-scale genome-wide association studies (GWAS) – a type of genetic research that makes statistical links between different disease states and widely shared variations in genetic code.
Ultimately, the Desiccan team was able to analyze the combined effect of such genetic markers on cardiovascular disease risk – based on five GWAS studies of more than 1 million people – and the risk of Alzheimer's – based on three GWAS studies of nearly 30,000 Alzheimer's patients And more than 50,000 age controls.
"Our approach works by combining and leveraging massive GWAS studies to make discoveries that are not usually invisible," Desiken said. "We are actually asking statistical power."
This analysis allowed researchers to identify 90 places in the genome where specific DNA versions increased the patients' combined chance of developing both Alzheimer's disease and the high blood levels of lipid molecules, including HDL cholesterol, LDL and triglycerides, which are common risk factors for cardiovascular disease.
The researchers confirmed that six of the 90 regions had the strongest effects of a "wide genome" on Alzheimer's levels and high lipid levels, including a number of genes that were never associated with the risk of dementia. These included several sites within the CELF1 / MTCH2 / SPI1 region on chromosome 11, which previously had been associated with the biology of the immune system.
However, although patients diagnosed with Alzheimer's frequently exhibit other cardiovascular risk factors, such as unhealthy levels of abdominal fat, type 2 diabetes, chest pain, or other symptoms of coronary artery disease, the researchers found no clear genetics between Alzheimer's disease and risk factors these.
The results of the study show that Alzheimer's and cardiovascular disease can also be affected by genetic factors that impair the ability of the body to process fats properly, "said first author Iris Bruce-Diaz, a postdoctoral doctor at Desiccan's lab. Other cardiovascular risks are not expected due to widespread genetics, although they can be linked to diet or other lifestyle factors.
"It's exciting because we know that cholesterol levels and other fats in the blood can be altered by changes in diet or drugs," Bruce added. "This raises the possibility that we may be able to help delay or even prevent the onset of Alzheimer's in these patients, although we will need more data before we can say that safely."
The Duke team examined whether healthy individuals with a family history of Alzheimer's disease were more likely to tolerate these new genetic variants, a relatively new method for studying the early risk factors of Alzheimer's called "Alzheimer's by proxy." The researchers found that these variants were more likely to be present in the genome of 50,000 people, one or more of whom had Alzheimer's disease, than nearly 330,000 without a family history of the disease.
"In healthy adults with a family history of Alzheimer's, a subset of cardiovascular risk factors strongly influence the risk of developing Alzheimer's disease," the authors write. "This is exactly the population we need to learn to see if reducing the risk of cardiovascular disease through lifestyle or medication can delay or prevent the onset of dementia later in life."
The researchers confirmed their findings in collaboration with Celeste M. Karch, PhD, an Alzheimer's specialist at the University of Washington School of Medicine in St. Louis. Kerch's team showed that the new genes associated with the risk of Alzheimer's / cardiovascular disease in the new study were expressed differently in the brains of Alzheimer's patients than in the control brain.
"This study emphasizes that we need to think about Alzheimer's in a holistic way," Kerch said. "There's a lot to learn about how genes that drive the risk of Alzheimer's disease also cause a change in the whole body."
"This is also an exciting opportunity because we already know a lot about these cardiovascular features and how to target them," she added.
Desikan and Broce-Diaz are now integrating these findings into the previously developed risk-based risk group that will allow physicians to calculate, based on the patient's genome, their combined risk for cardiovascular disease and Alzheimer's disease. The researchers hope that their work will help launch a precise medical approach to test lipid levels in people with new risk factors, whether by diet or by established drugs such as statins, that may delay or prevent the onset of Alzheimer's disease.
"That's really the goal," said Bruce-Diaz. "If we can identify the subgroups whose cardiovascular customers are genetically linked, we think there is a possibility that lowering blood lipids can help reduce the risk of developing dementia later in life, such treatments have not worked in clinical trials before, but it could be that not We had a good way of choosing who would benefit from their genetics. "