A rare variant of a gene called RAB10 provides a protective effect for high-risk individuals — elderly people who carry known genetic risk factors for Alzheimer’s — who never acquired the disease, a study from Brigham Young University has found.
This means there is specific reason why people who should get Alzheimer’s remain healthy. Study authors believe this genetic function could be targeted 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,” “And we were able to identify a promising genetic variant.”
said Perry Ridge, assistant professor of biology at BYU, who co-led the study with professor John Kauwe.
That former approach to Alzheimer’s disease has been generally effective in producing a list of genes that might impact risk for the disease, but it leaves researchers without sufficient data on what to do next. In this new approach, Ridge and Kauwe develop the biological mechanism by which a genetic variant actually impacts Alzheimer’s disease.
Using data from the Utah Population Database — a 20-million-record database of the LDS Church’s genealogical records combined with historical medical records from Utah — Ridge and Kauwe first identified families that had a large number of resilient individuals: those who carried the main genetic risk factor for Alzheimer’s (E4 Allele) but remained healthy into advanced age.
With whole genome sequencing and a linkage analysis methodology, they then looked for the DNA that those resilient individuals shared with each other that they didn’t share with loved ones who died of Alzheimer’s.
They discovered the resilient subjects shared a variant in the RAB10 gene, while those who got the disease did not share the genetic variant.
Once the researchers identified the potentially protective gene variant, they over-expressed it in cells and under-expressed it in cells to see the impact on Alzheimer’s disease-related proteins. They learned that when this gene is reduced in your body, it has the potential to reduce your risk for Alzheimer’s.
“There are currently no meaningful interventions for Alzheimer disease; No prevention, no modifying therapies, no cure,” Kauwe said. “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.”
The work was supported by the National Institute on Aging, National Institute of Neurological Disorders and Stroke, and Mayo Clinic Center for Individualized Medicine. Additional supported by access to equipment was made possible by the Hope Center for Neurological Disorders, and the Departments of Neurology and Psychiatry at Washington University School of Medicine.
Perry G. Ridge, et al. Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer’s disease resilience Genome Medicine 20179:100
Last Updated on November 11, 2023