A study comparing genetic markers in the DNA of people with and without Alzheimer’s disease identified a common gene that appears to increase a person’s risk for developing the disease. The finding suggests that the gene GAB2 modifies an individual’s risk when associated with other genes, including APOE4. The study results appear in the June 7 issue of Neuron.
To date, the most significant gene found to predispose an individual to late-onset Alzheimer’s 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.
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 the gene 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.
Kronos Science Laboratory, which funded the study, plans to use this study to develop a test that aids in clinical diagnosis and determining a person’s genetic predisposition for developing Alzheimer’s disease.