Researchers at Brigham and Women’s Hospital (BWH) continue to make important contributions to the advancement of further understanding the underlying causes of Alzheimer’s disease. After last week’s announcement that BWH scientists have determined that decreased brain activity is linked to a decline in the ability to conduct daily tasks associated with Alzheimer’s, the institution has followed up with a news release offering new findings from the first large-scale Alzheimer’s study that used an epigenome-wide association study (EWAS) approach to looking at the brain’s chromosomal make-up and how it relates to those with Alzheimer’s disease.
Dr. Philip L. De Jager, a researcher for the Program in Translational Neuropsychiatric Genomics, BWH Departments of Neurology and Psychiatry, and the study’s lead author said, “Our study approach may help us to better understand the biological impact of environmental risk factors and life experiences on Alzheimer’s disease,” and adding that, “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.”
The study, which was conducted in partnership with researchers from Rush University Medical Center, used EWAS to process DNA data taken from analysis of 708 brains that were donated for scientific study by the Religious Orders Study and the Rush Memory and Aging Project, which was led by study co-author, Dr. David A. Bennett from the Rush Alzheimer’s Disease Center in Chicago. After an analysis of the donated brains, the research team discovered that early changes in DNA methylation — a key indicator of active DNA in the human genome that signals a biochemical alteration in the building blocks of genetics — directly relates to the onset of Alzheimer’s.
Specifically, researchers revealed that DNA methylation levels were found to correlate with people who had been diagnosed with Alzheimer’s disease in 71 of 415,848 CpG markers that were analyzed, which were located in the RHBDF2, ANK1, ABCA7, and BIN1 genes. All of these gene types are closely associated with Alzheimer’s disease.
In addition, analysis of these newly-discovered CpG associations also revealed other genes that featured altered RNA expression in the brain samples, including CDH23, RHBDF2, DIP2A, RNF34, RPL13, and SERPINF1/SERPINF2. The findings suggest that these CpG associations point to altered genes found in Alzheimer’s.
The study, entitled, “Alzheimer’s disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci,” was published on August 17th, 2014 online in the journal Nature Neuroscience, and was supported by the NIH, along with the Siragusa Foundation, the Alzheimer’s Research UK, and the Robert and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program.