Researchers from Rush University Medical Center and Brigham and Women’s Hospital (BWH) conducted a study recently demonstrating how an epigenetic alteration to DNA of the brain is connected to Alzheimer’s disease. The team looked at DNA methylation, which is an epigenetic mechanism that occurs when a methyl group is added to the cytosine or adenine of DNA. This epigenetic mechanism, as well as others such as DNA demethylation and histone acetylation, have the ability to turn on or off genes.
According to the team of researchers, their study in Nature Neuroscience is the first to carry out a large-scale investigation of the brain and Alzheimer’s using epigenome-wide association studies (EWAS), which compare chromosomal changes and can identify loci associated with common diseases. According to the Alzheimer’s Foundation of America, about 5.1 million Americans may have Alzheimer’s disease and it’s continuing to rise in line with the aging population. It commonly affects those after age 65 but can also occur as early onset or young onset Alzheimer’s.
Philip L. De Jager, MD, PhD, Program in Translational Neuropsychiatric Genomics, BWH Departments of Neurology and Psychiatry, lead study author explained: “Our study approach may help us to better understand the biological impact of environmental risk factors and life experiences on Alzheimer’s disease. There are certain advantages to studying the epigenome, or the chemical changes that occur in DNA. The epigenome is malleable and may harbor traces of life events that influence disease susceptibility, such as smoking, depression and menopause, which may influence susceptibility to Alzheimer’s and other diseases.”
Using 708 brain samples that were donated from individuals in the Religious Orders Study and Rush Memory and Aging Project, the researchers assessed methylation levels and their association with Alzheimer’s. They discovered 71 out of 415,848 CpGs correlated with Alzheimer’s. The 71 markers were in ANK1, RHBDF2, BIN1 and ABCA7 genes, the last two of which are known to contain Alzheimer’s disease susceptibility variants. They then validated 11 of the differentially methylated regions using 117 subjects from an independent set.
Looking at the CpG associations further, the researchers found genes nearby with altered RNA expression in the Alzheimer’s brain samples: ANK1, CDH23, DIP2A, RHBDF2, RPL13, RNF34, SERPINF1 and SERPINF2. These data propose that the function of the identified genes are altered in those with Alzheimer’s.
De Jager explains “because these findings are also found in the subset of subjects that are not cognitively impaired at the time of death, it appears that these DNA methylation changes may play a role in the onset of Alzheimer’s disease. Moreover, our work has helped identify regions of the human genome that are altered over the life-course in a way that is associated with Alzheimer’s disease. This may provide clues to treating the disease by using drugs that influence epigenomic function.”
Source: Learn all about it and read more about their findings here: Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Philip L De Jager et al. August 2014.
References: Bringham and Women’s Hospital. DNA Methylation Involved in Alzheimer’s. August 2014.
Alzheimer’s Foundation of America. http://www.alzfdn.org/AboutAlzheimers/statistics.html. June 2014.