PHOENIX, June 6, 2007 -- A study comparing more genetic markers in the DNA of people with and without Alzheimer’s disease than ever before has enabled researchers to identify a common gene that appears to increase a person’s risk for developing Alzheimer’s disease. The finding, announced today by researchers at the Translational Genomics Research Institute (TGen), Banner Alzheimer’s Institute, Kronos Science Laboratory and their collaborative partners, suggests that the gene — called GAB2 — modifies an individual’s risk when associated with other genes, including APOE4. The study results appear in the June 7 issue of the prestigious peer-reviewed journal, Neuron.
Alzheimer’s disease is the most common form of disabling memory and thinking problems in older people. The progressive neurological disorder afflicts an estimated 5 million Americans, a number expected to triple by 2050.
“We have entered a new era in medical research. Today’s technologies permit us to survey a sufficient number of letters throughout the human genome to provide a clearer picture of how life works and ultimately allow better clinical management of patients,” said Dr. Dietrich Stephan, Director of TGen’s Neurogenomics Division and the paper’s senior author, “These new, robust tools may eventually allow us to improve our ability to diagnose Alzheimer’s disease, even before it strikes”
To date, the most significant gene found to predispose an individual to late onset Alzheimer’s (LOAD) has been APOE4. In this latest study, researchers from seven organizations contributed to the genome-wide scan using Affymetrix microarray technology. The team screened the DNA from 1,400 individuals who had been clinically assessed with Alzheimer’s prior death, and simultaneously examined more than 500,000 SNPs or genetic variations to characterize and confirm additional LOAD susceptibility genes. The search revealed GAB2.
Based on the genetics of this and other neuroscientific findings, researchers suggest the healthy form of the GAB2 gene may protect brain cells from developing tangles, one of the hallmarks of Alzheimer’s disease. If the findings are confirmed, this discovery could provide a target for future Alzheimer’s therapeutic drugs.
“We hope that this study, along with the genome-wide genetics studies to come, will contribute to the clarification of Alzheimer’s risk factors and disease mechanisms, the discovery of promising new disease-slowing and prevention therapies, and the identification of patients and at-risk people most likely to benefit from those treatments,” said Dr. Eric Reiman, the study’s first author and Executive Director of the Banner Alzheimer’s Institute.
After finding an association between a form of the GAB2 gene and Alzheimer’s disease in three separate groups, the researchers showed that the GAB2 gene is unusually active in vulnerable brain cells from Alzheimer’s patients and that the GAB2 protein produced by this gene is present in those brain cells containing tangles. When the researchers silenced GAB2 in preliminary studies it increased a molecular process thought to play an important role in the development of tangles. Based on these findings, the researchers hypothesize that GAB2 might function under normal conditions to compensate for the harmful effects of APOE4 and other genes in older people and that the GAB2 risk gene lacks this protective effect.
The study, funded by Kronos Science Laboratory, an affiliate of Phoenix-based Kronos Optimal Health Company, will enable Kronos to develop a test that aids in clinical diagnosis and help determine a person’s genetic predisposition for developing Alzheimer’s disease.
“This discovery allows us to accelerate the development process for creating a new diagnostic test that is capable of detecting the presence of GAB2, and may ultimately help millions of individuals reach a more informed decision regarding the most appropriate type and timing of treatment,” said Dr. Chris Heward, President of Kronos Science Laboratory.
Until recently, researchers lacked the technology to examine the genetic components of a disease at such a high-level of detail. By utilizing the Affymetrix 500K Arrays, the study’s researchers rapidly produced a genetic map of each brain tissue sample and isolated the GAB2 gene relatively quickly.
“This Alzheimer's disease breakthrough is another powerful example of a fundamental life science discovery made by an Affymetrix customer. Our latest microarray technology continues to accelerate research at an unprecedented pace by enabling scientists to better identify the specific genetic variations associated with complex diseases,” said Kevin King, President of Life Sciences Business and Executive Vice President at Affymetrix.
In addition to surveying an unprecedented number of genetic markers in each person’s DNA, the researchers capitalized on extremely rigorous criteria to determine whether or not their volunteers had Alzheimer’s. For instance, the study included more than 1000 brain donors confirmed to either have Alzheimer’s disease or be free of the disorder at autopsy. This study resulted in a comprehensive set of high-quality data to be made publicly available to the research community. The researchers believe that deposition of this data set in the public domain will open a new era in Alzheimer research. When a scientist suspects a particular gene or pathway maybe implicated in Alzheimer’s disease, they will use these data to see if there is genetic evidence supporting their idea. Reviewing these data in an hour will permit them to save months of work and thousands of dollars to achieve the same result. Moreover, it paves the way for even more advanced studies using larger sample populations, more powerful array chips that can distinguish more genetic markers, and more sophisticated methods of analyzing the data.
Study participants included TGen, Kronos Science Laboratory, Banner Alzheimer’s Institute, Mayo Clinic Scottsdale, the Netherlands Brain Bank, Sun Health Research Institute, and the Alzheimer’s Disease Centers of the National Institutes of Health’s National Institute of Aging.
The Translational Genomics Research Institute (TGen), a non-profit 501(c)(3) organization, is focused on developing earlier diagnostics and smarter treatments. Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases. TGen’s research is based on personalized medicine and the institute plans to accomplish its goals through robust and disease-focused research. www.tgen.org
About Banner Alzheimer’s Institute
The Banner Alzheimer’s Institute is a non-profit 501(c)(3) organization that provides comprehensive clinical care for patients with memory and thinking problems; education, referral and support services for family and caregivers; and leading-edge research in clinical trials, brain imaging and genetics studies. The Institute is devoted to finding Alzheimer’s disease-slowing and prevention treatments in the shortest time possible.
Kronos Science Laboratory (KSL) is a specialty clinical reference/research laboratory that explores and develops new and improved assays for the measurement of aging and early diagnosis of age-related diseases. Opened to the medical and scientific communities in 1999, the Phoenix-based laboratory offers collaborative and contract research services specializing in custom assay development, test validation, testing services, pharmacokinetics, and clinical trial experimental design. KSL provides specialty laboratory services to physicians, pharmaceutical companies, biotechnology companies and other organizations engaging in clinical trials and basic research. KSL is licensed in 49 states and is committed to compliance with all applicable regulatory guidelines and accrediting standards including, but not limited to, CLIA, GCP, GLP and CMS. KSL, the Kronos Optimal Health Company (worksite wellness programs) and the Kronos Optimal Health Centre (executive health and personalized wellness programs) together provide an integrated health care delivery system designed to optimize human health and longevity. For more information, visit www.KronosHealth.com or www.KronosLaboratory.com.
Affymetrix GeneChip® microarray technology is the industry-standard tool for analyzing complex genetic information. After inventing microarray technology in the late 1980s, Affymetrix scientists have been dedicated to developing innovative products that provide researchers with a more complete view of the genome. These products continue to accelerate genetic research and enable scientists to develop diagnostics and tailor treatments for individual patients by identifying and measuring the genetic information associated with complex diseases.
Today, Affymetrix technology is used by the world’s top pharmaceutical, diagnostic and biotechnology companies, as well as leading academic, government and not-for-profit research institutes. More than 1,500 systems have been shipped around the world and more than 8,500 peer-reviewed papers have been published using the technology. Affymetrix Inc. (NASDAQ: AFFX) is headquartered in Santa Clara, Calif., and has manufacturing facilities in Sacramento, Calif. and Singapore. The company has about 1,100 employees worldwide and maintains sales and distribution operations across Europe and Asia. For more information about Affymetrix, please visit the company’s website at www.affymetrix.com.
Banner Alzheimer’s Institute
Christopher B. Heward, Ph.D.