Mutation in immune system gene linked to Alzheimer's disease

An international research team including scientists from the University of Toronto’s Faculty of Medicine has discovered a link between a mutation in an immune system gene and Alzheimer’s disease.

“This discovery provides an increasingly firm link between brain inflammation and increased risk for Alzheimer’s,” said Dr. Peter St George-Hyslop, director of U of T’s Tanz Centre for Research in Neurodegenerative Diseases.

Using data from 25,000 people, researchers from the Faculty of Medicine and University College London’s Institute of Neurology discovered that a rare genetic mutation in the TREM2 gene — which helps trigger immune system responses — is also associated with increased risk of Alzheimer’s. The discovery supports an emerging theory about the role of the immune system in the disease.  

“This is an important step towards unraveling the hidden causes of this disease," St George-Hyslop said, "so that we can develop treatments and interventions to end one of the 21st century’s most significant health challenges.”

St George-Hyslop, renowned for identifying five genes associated with Alzheimer’s disease, said the breakthrough is, “another win for U of T scientists who are building on a worldwide legacy of expertise in neurodegenerative research.”

The team began by sequencing the genes of 1,092 people with Alzheimer’s and a control group of 1,107 healthy people. The results showed several mutations in the TREM2 gene occurred more frequently in people who had the disease than in those without the disease. One mutation – known as R47H – had a particularly strong association with the disease.

The mutation makes a patient three times more likely to develop the disease, although it affects just 0.3 per cent of the population.

“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,” said Dr. Rita Geurreiro from UCL, the study’s lead author.

The study is published now in the New England Journal of Medicine.