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.