October 28, 2013
International Team Finds 11 New Alzheimer’s Genes
In the biggest international study ever conducted on Alzheimer's disease, the International Genomics Alzheimer's Project (I-GAP) consortium has found eleven new regions of the genome involved in the onset of the neurodegenerative disorder.
The project involved searching the DNA of over 74,000 volunteers for new genetic risk factors linked to late-onset Alzheimer's disease, the most frequently seen form of the disease. I-GAP, made up of four research consortia in the United States and Europe, made the discovery possible via thousands of DNA samples and shared datasets"Collaboration among researchers is key to discerning the genetic factors contributing to the risk of developing Alzheimer's disease," said Dr. Richard J. Hodes, director of the National Institute on Aging (NIA) . "We are tremendously encouraged by the speed and scientific rigor with which IGAP and other genetic consortia are advancing our understanding."
One of the biggest finds was the HLA-DRB5/DRB1 region, which plays a role in the body’s immune system and inflammatory response. This region of genome has been connected with multiple sclerosis (MS) and Parkinson's disease, indicating that the diseases where irregular proteins build up in the brain may have a common system involved, and possibly a common target for treatment.
"The discovery of novel pathways is very encouraging considering the limited success of Alzheimer's disease drugs tested so far," said Dr. Margaret Pericak-Vance, Director of the Miami Institute of Human Genomics. "Our findings bring us closer toward identifying new drug targets for Alzheimer's and other neurodegenerative diseases.”
The study also reported another 13 genetic variants that should be analyzed further.
"Interestingly, we found that several of these newly identified genes are implicated in a number of pathways," said Gerard Schellenberg, from the University of Pennsylvania School of Medicine. "Alzheimer's is a complex disorder, and more study is needed to determine the relative role each of these genetic factors may play. I look forward to our continued collaboration to find out more about these—and perhaps other—genes."
"This study clearly demonstrates that there really is strength in numbers to identify genes that individually have a small effect on risk of Alzheimer's," said Lindsay A. Farrer, Chief of Biomedical Genetics at Boston University Medical Center."But it's not the magnitude of the odds ratio that's really important.”
“Each gene we implicate in the disease process adds new knowledge to our understanding of disease mechanism and provides insight into developing new therapeutic approaches, and ultimately these approaches may be more effective in halting the disease since genes are expressed long before clinical symptoms appear and brain damage occurs,” he added.
"This landmark international effort has uncovered new pathways and new genes in old pathways that are definitely associated with Alzheimer dementia, but we need to do much work to better understand how exactly these genes work in health and disease, and to perhaps make drugs from these genes and molecules," said Dr. Sudha Seshadri, professor of neurology at Boston University School of Medicine.
"We will continue to mine these results for new insights, even as we include more patients and use new technologies like whole genome sequencing to find more new pathways and genes.”