Scientists at BYU and several other leading Alzheimer’s research institutions have discovered a rare genetic mutation that increases the risk of Alzheimer’s disease.
The international team of researchers report in this week’s issue of the New England Journal of Medicine that a rare variant of TREM2, a gene associated with the immune system, is linked to a higher risk of Alzheimer’s.
The study, which used genetic data from more than 25,000 people, suggests that problems with the immune system could be a key player in the development of Alzheimer’s.
“Discovering a new gene for Alzheimer’s disease is major step in learning about the genes, proteins and biological pathways that actually cause disease,” said BYU geneticist John “Keoni” Kauwe, a co-author on the study. “And that’s what we need to know to come up with ways to prevent or cure Alzheimer’s.”
Treatments for the disease have been unsuccessful because by the time a person is diagnosed, the disease has already been crippling the brain for years. Scientists like Kauwe are doing the science behind future diagnostic tests that will hopefully predict Alzheimer’s five, 10 or 15 years before onset.
Kauwe’s BYU team provided the initial validation of the discovery and contributed more than 200 complete human genomes to the study. Ph.D. student Perry Ridge did the analysis of the whole genome sequence data using BYU’s Fulton Supercomputing Center.
For now, the causes of Alzheimer’s are unknown. In an effort to get a clearer picture of the causes of the disease, Kauwe and other researchers set out to uncover some of the rarer genetic variants associated with Alzheimer’s.
Researchers first sequenced the genes of 1,092 people with the disease and a control group of 1,107 healthy people. Results showed mutations in a gene named “TREM2” occurred more frequently in those with Alzheimer’s.
The team then confirmed their findings by analyzing data from the genes of an additional 23,000 people. They once again found that a certain variant in the TREM2 gene was more likely to appear in people with Alzheimer’s.
“These findings are particularly exciting because they give us a clear signal about what could be going wrong in Alzheimer’s disease,” said study lead author Rita Guerreiro. “While the genetic mutation we found is extremely rare, its effect on the immune system is a strong indicator that this system may be a key player in the disease.”
While the mutation Kauwe and his colleagues discovered increases the likelihood of developing Alzheimer’s roughly three-fold, it is extremely rare, affecting just 0.3% of the population.
But by identifying the mutation, the research provides valuable new information about the potential causes of Alzheimer’s disease.
“While genetics doesn’t immediately lead to a cure, we have provided and are continuing to provide the foundation of information that’s necessary to cure this disease,” Kauwe said. “And we just didn’t have that five years ago. Over the next ten years we are going to make progress that will make a difference to those dealing with this disease.”
BYU, along with University College London, Washington University and the National Institute of Health made up the core group who led the study.