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RAB10

Scientists Find Gene That Protects Against Alzheimer’s in High-Risk Population

By | November 30th, 2017

November 30, 2017

In a new study, scientists have identified a gene that protects against Alzheimer’s in those who are at a high-risk of dementia—elderly people with a genetic variant known as ApoE4. Statistically, these people are at the highest risk of developing Alzheimer’s. But a small subset of them never do, and scientists say that’s thanks to a variant in a gene called RAB10.

Researchers have known for a long time that carrying a gene called ApoE4 increases risk of Alzheimer’s disease. If you have one copy of the gene, your risk of Alzheimer’s goes up three times. If you have two copies, it increases twelvefold. For someone with two copies who lives to 65, that’s a 91 percent chance of developing late-onset Alzheimer’s.

“Instead of identifying genetic variants that are causing disease, we wanted to identify genetic variants that are protecting people from developing disease,” said Perry Ridge, assistant professor of biology at BYU. “And we were able to identify a promising genetic variant.”

Scientists from Brigham Young University took data from the Utah Population Database—records kept by the Mormon church on geneology and historical medical history that number around 20 million—and used it to identify families that had a large number of ApoE4 carriers, but a lower incidence of Alzheimer’s. They then looked at the DNA of individuals who didn’t develop Alzheimer’s in comparison with their relatives who did. That’s when the variant in RAB10 emerged as the differentiating factor.

Once the team identified the gene variant, they took it to the lab, where they tried increasing it and decreasing it in cells to see how it would affect the proteins that are associated with Alzheimer’s disease. They found that decreasing this variant also decreased the Alzheimer’s-related proteins, meaning it may have the potential to reduce Alzheimer’s disease.

“There are currently no meaningful interventions for Alzheimer disease; no prevention, no modifying therapies, no cure,” study author John 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.”

This study was published in the journal Genome Medicine.

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