by Summary: Researchers have discovered new genetic variants associated with Alzheimer’s disease risk, which could pave the way for a predictive blood test. The study, which focused on the APOE gene, identified 15 new mutations associated with Alzheimer’s.
These findings delve into the complex network of factors that contribute to the disease. This new information could greatly help diagnose Alzheimer’s even before symptoms appear.
Key facts:
- The study identified 15 new mutations in the regions of the APOE gene and other parts of the genome that are linked to the risk of Alzheimer’s disease.
- The APOE-4 variant of the ApoE molecule is among the highest genetic risks for Alzheimer’s, while the APOE-2 variant appears to be protective.
- Low plasma levels of ApoE are associated with increased risks of Alzheimer’s, dementia, and dementia.
Source: At the University of Pittsburgh
Researchers at the University of Pittsburgh are analyzing thousands of human genomes to find new gene variants responsible for controlling levels of blood plasma molecules associated with the risk of Alzheimer’s disease.
The results, published recently in the Molecular Psychiatry, may contribute to the future development of simple blood tests for this disease.
Led by Ilyas Kamboh, Ph.D., professor of human genetics and epidemiology at Pitt Public Health, the team found that, in addition to the known genetic variants associated with disease risk, there are at least 15 more variants in APOE, or Apolipoprotein. E, the gene and other parts of the genome can affect the possibility of Alzheimer’s, although more research is needed to make clear conclusions.
Alzheimer’s disease is one of many diseases with thousands of factors affecting it. In addition to the common symptoms of Alzheimer’s disease, such as amyloid plaques and tau tangles, many other factors contribute to whether a person will develop the disease at some point in their life.
One of the most interesting things about human DNA is how stable and highly variable it is at the same time. Some genes encoded in DNA have two or more different forms, called polymorphisms, which usually differ by only a few letters of the DNA alphabet. While some of these genetic variants are benign and do not affect gene function, others may predict disease risk.
Polymorphisms in the APOE gene are one such example. Among the genetic markers that confer the greatest risk of Alzheimer’s disease is APOE-4, the precursor of the gene encoding the ApoE molecule. The APOE-2 variant, on the other hand, appears to be protective.
In brain tissue, ApoE supports neurons by providing them with fat-soluble nutrients, including cholesterol and fat-soluble vitamins, needed for neurodevelopment and repair. ApoE is also abundant in the blood, where it transports cholesterol and other substances to various parts of the body. Low plasma ApoE appears to be associated with a higher risk of Alzheimer’s disease, cognitive impairment and dementia.
In a study that looked at the genomes of more than 2,500 adults, Kamboh and his team found that, in addition to the APOE types that have been described, eight previously unknown changes in the regions of the APOE gene are associated with variations in plasma ApoE levels, a risk. Alzheimer’s disease and the deposition of toxic amyloid in the brain. Further analysis found seven novel mutations in non-APOE regions of the genome that account for additional changes in plasma ApoE levels.
While further animal studies are needed to make definitive conclusions about the link between plasma ApoE genes and a possible mechanistic link to Alzheimer’s disease, the researchers hope that their understanding can help inform the development of future blood biomarkers for Alzheimer’s disease.
“The field has made progress in developing diagnostic methods that detect Alzheimer’s risk in blood samples from people who have not developed symptoms of the disease,” Kamboh said. “One day, plasma ApoE may be a significant addition to the panel of biomarkers that will be used to inform physicians about the diagnosis of their patients.”
Other authors of the study are M. Muaaz Aslam, Ph.D., Kang-Hsien Fan, Ph.D., Elizabeth Lawrence, BS, Margaret Anne Bedison, BS, Beth Snitz, Ph.D., Oscar Lopez, MD, Eleanor Feingold, Ph.D., all from Pitt; and Steven DeKosky, MD, of the University of Florida.
About this gene and Alzheimer’s disease research news
Author: Anastasia Gorelova
Source: At the University of Pittsburgh
Contact: Anastasia Gorelova – University of Pittsburgh
Image: Image attributed to Neuroscience News
Original Research: Open access.
“Genome-wide analysis identifies novel loci affecting plasma apolipoprotein E concentration and Alzheimer’s disease risk” by Ilyas Kamboh et al. Molecular Psychiatry
Abstract
Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer’s disease risk.
I APOE 2/3/4 polymorphism is the major genetic risk factor for Alzheimer’s disease (AD). This polymorphism is also associated with variation in plasma ApoE levels; while APOE*4 turn down, APOE*2 increases the level of ApoE. A low plasma level of ApoE has also been suggested as a risk factor for dementia.
To our knowledge, no large genome-wide association study (GWAS) has been reported on plasma ApoE level.
This study aims to identify new genetic variants affecting plasma ApoE and to evaluate whether the baseline ApoE level is associated with cognitive function and incident dementia in a long-term cohort of the Ginkgo Evaluation of Memory (GEM) study.
Baseline plasma concentrations of ApoE were measured in 3031 participants (95.4% European Americans (EAs)). A GWAS analysis was performed on 2580 self-identified EAs for which both genotype and plasma ApoE data were available.
Lower ApoE concentrations were associated with poorer cognitive function, but not with incident dementia. As expected, the risk of AD increased from E2/2 to E4/4 genotypes (P for trend = 4.8E-75). In addition to confirming the expected and negative associations of APOE*2 (P = 4.73E-79) and APOE*4 (P = 8.73E-12) and ApoE level, GWAS analysis revealed nine additional traits independent of APOE region, and together they explain about 22% of the variation in plasma ApoE level.
We also identified seven new loci on chromosomes 1, 4, 5, 7, 11, 12 and 20 (Prange = 5.49E-08 to 5.36E-10) explaining about 9% of the variance in ApoE level.
Plasma ApoE correlates with different independent levels, especially in APOELocally, they were associated with the risk of AD and amyloid deposition in the brain, suggesting that variation in ApoE levels may be genetically determined as a risk factor for developing AD.
These findings improve our understanding of the genetic determinants of ApoE plasma levels and their potential value in influencing AD risk.
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