Research from North Carolina State University suggests that changes to certain areas of the genome, called imprint control regions, during early development may increase the risk of developing Alzheimer’s disease. This study also indicates that Black individuals may be more susceptible to these changes compared to white individuals. This research enhances our knowledge of how environmental factors can impact the development of Alzheimer’s disease.The type of environmental factors that can play a role in genetic changes and susceptibility to diseases.
Cathrine Hoyo, a professor of biological sciences at NC State and co-corresponding author of the research, suggests that genetics sets the stage for disease, but it is environmental factors that trigger it. The Institute of Medicine estimates that how our genes respond to the environment, known as epigenetic response, contributes to 70% to 90% of chronic disease risk. And for Alzheimer’s disease, only about 5% of the cases are solely due to genetics.f cases of Alzheimer’s are inherited, while others are non-familial or sporadic. According to Hoyo, the risk of developing non-familial Alzheimer’s varies by race, with Black people having twice the incidence of white people. The research aimed to identify stable epigenetic features in Alzheimer’s brains that are unlikely to change once established. Specifically, the team used the imprintome, which consists of imprint control regions (ICRs) in the human genome that regulate the expression of imprinted genes, to find these stable epigenetic features.Tags and formatting will remain unchanged, but the text will be presented in a more easily understandable way:
The study distinguished individuals with Alzheimer’s disease from those without.
Imprinted genes are unique from other genes because only one parental copy of an imprinted gene is active, while the other copy is methylated, or silenced, early in development. In addition, the methylation marks that regulate their expression can be influenced by the environment.
“Imprinted genes do not have a backup copy in case of mutation,” explains Randy Jirtle, professor of epigenetics at NC State and co-corresponding author of the research. “ICRs control the expression of these genes, essentially informing imprinted genes where,The process of DNA methylation should be addressed and understood. The methylation marks in ICRs typically remain unchanged unless modified early in development, such as at conception or shortly after. The research involved brain tissue samples from 17 donors, including eight normal brains and nine with Alzheimer’s. The samples were divided between non-Hispanic white and non-Hispanic Black donors, with five samples from Black donors and four from white donors in the Alzheimer’s group. The team conducted whole-genome sequencing for each sample and then examined the ICRs in the Alzheimer’s brains that were either over- or under-methylated.Comparing the brains of individuals with Alzheimer’s disease to those of healthy individuals, researchers discovered 120 differently methylated ICRs. Of these, 40 were found in both Black and white populations, while 81 were only found in the Black population and 27 were only found in the white population. The commonly methylated ICRs in both populations are linked to the genes MEST/MESTIT1 and NLRP1, which are involved in brain inflammation and are potential disease markers. This discovery of common ICRs could lead to the development of universal tests for identifying disease markers.It is quite surprising to find that the Black population had nearly three times as many affected ICRs as the white population.
“When you observe such a significant difference, and you understand that the changes you’re identifying are likely the result of early environmental interactions, one possible explanation is that there are distinct or different stressors in that population, and those epigenetic effects are being inherited.”
The researchers are optimistic that the findings could lead to the development of testing and specific early interventions to prevent Alzheimer’s disease.
“We are aware that targeted prevention over extended periods can modify the risk.”According to Hoyo, early alert systems for identifying disease risk and implementing targeted interventions could potentially prevent the onset of disease. Jirtle believes that epigenetics offers hope, as changes in the epigenome could potentially counteract disease risks, even though genetic mutations cannot be reversed. The study, published in Clinical Epigenetics, received support from the National Institutes of Health through various grants. Brain tissue samples were provided by Duke University School of Medicine, and former NC State Ph.D. student Sebnam Cevik contributed to the research.NC State researchers, including Sebnem E. Cevik, David A. Skaar, and Antonio Planchart, along with Ph.D. student Dereje Jima, conducted a study on DNA methylation of imprint control regions associated with Alzheimer’s disease. Duke University School of Medicine contributors to the work included Dr. Andy Liu, Dr. Truls Østbye, and Dr. Heather E. Whitson.
