Researchers think they've found a gene that could help better predict a person's risk of developing Alzheimer's disease.
The gene -- called GAB2 -- seems to modify an individual's risk of developing the progressive neurological disease, when associated with other genes, including APOE4, according to the research team led by the Translational Genomics Research Institute and Banner Alzheimer's Institute in Arizona..
The study results appear in the June 7 issue of the peer-reviewed journal, Neuron.
"This is a major breakthrough in Alzheimer's genetic research that will have an impact on the clinical treatment of the disease," said Dr. Dietrich Stephan, director of TGen's neurogenomics division.
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.
Researchers are not sure what causes Alzheimer's. They do know that sufferers' brains are harmed by plaques and tangles that block signals and ultimately cause cells to shrink and die.
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 screened the DNA from 1,400 individuals who had been clinically assessed with Alzheimer's prior to death. They also 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.
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 the vulnerable brain cells of Alzheimer's patients. They also noticed that the GAB2 protein produced by this gene is present in those brain cells containing tangles.
When the researchers silenced GAB2, 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.
