Scientists have identified a gene variant that, if reduced, may decrease the risk of Alzheimer’s disease.
Researchers from Brigham Young University (BYU) have discovered a rare genetic variant that provides a protective effect for high-risk individuals, including elderly people who carry known genetic risk for Alzheimer’s but never acquire the disease.
The researchers believe they can target the genetic function with drugs to help reduce the risk of people getting the disease.
“Instead of identifying genetic variants that are causing disease, we wanted to identify genetic variants that are protecting people from developing disease,” Perry Ridge, a professor in The College of Life Sciences at BYU, said in a statement. “And we were able to identify a promising genetic variant.”
The former approach to Alzheimer’s disease has been generally effective in producing a list of genes that might affect risk for the disease. However, researchers do not have the sufficient data on what to do after the genes are identified.
The researchers have now developed the biological mechanisms by which a genetic variant actually affects Alzheimer’s.
They used data of 200 Alzheimer’s resilient individuals and a pedigree-based approach to identify genetic variants that segregate with Alzheimer’s resilience.
Using whole genome sequencing and a linkage analysis methodology, they then looked for the DNA that those resilient individuals shared with each other that they did not share with loved ones who died of Alzheimer’s. The researchers found that the resilient subjects shared a variant in the RAB10 gene, while those who acquired the disease did not share this gene variant.
After identifying the potentially protective gene variant, the researchers over expressed it in cells and under expressed it in cells to see the impact it had on Alzheimer’s disease-related proteins, and found that when the gene is reduced in the body, it may reduce the risk for the disease.
“There are currently no meaningful interventions for Alzheimer disease; No prevention, no modifying therapies, no cure,” John Kauwe, a professor in The College of Life Sciences at BYU, said in a statement. “The discoveries we’re reporting in this manuscript provide a new target with a new mechanism that we believe has great potential to impact Alzheimer’s disease in the future.”
According to the study, known Alzheimer’s markers do not explain the majority of genetic variance and are not helpful for predicting or diagnosing disease. A majority of remaining variants are likely to be rare and the functional consequences of known markers, or surrounding genetic variants, are unknown.
The study was published in Genome Medicine.
