Study Finds Mutation Related to Alzheimer’s

A newly discovered variant of the gene TREM2 greatly increases the risk of late-onset Alzheimer’s Disease for carriers of the mutation, according to a study completed in part by the Emory School of Medicine.

The finding, which was published in the New England Journal of Medicine on Nov. 14, is a result of a 10-year collaboration between the School of Medicine and deCODE genetics, a company in Iceland.

The variant is stronger than 10 other low-risk factors and comparable in strength to ApoE, the most common genetic risk factor for Alzheimer’s, according to Allan Levey, director of Emory’s Alzheimer’s Disease Research Center and chair of neurology at the Emory University School of Medicine.

The new gene is extremely rare, affecting only one out of every 200 people, Levey said.

However, it is notable because it greatly increases the risk of Alzheimer’s.

According to Levey, the findings indicate that inflammation of the brain plays an important role in causing Alzheimer’s because the variant of TREM2 blocks the gene’s usual anti-inflammatory effects.

The role of inflammation is significant because it informs researchers about the biological processes common to all forms of Alzheimer’s, even though only a few people carry the specific TREM2 mutation, Levey said.

Levey said he feels the strong evidence indicating inflammation as a cause of Alzheimer’s that will lead to further research of the effects of inflammation in the future.

Researchers reached these conclusions when looking at the genome sequences of Alzheimer’s patients in Iceland in an attempt to discover any genetic mutations associated with the disease, according the Levey.

The study, which included more than 100,000 controls and required extremely large samples of patients, found multiple genes that are associated with a risk of Alzheimer’s Disease.

These genes included ApoE, a second, lower-risk gene described in a study a few months ago and TREM2, which is the basis for the Nov. 14 publication.

Researchers compared Iceland’s isolated population to a population of Alzheimer’s patients at Emory, as well as patients in the Netherlands, Germany and Norway.

The study was able to associate the new TREM2 mutation with Alzheimer’s in all locations.

Levey said it is not yet known whether the mutation will be a risk factor for early-onset Alzheimer’s as well as late-onset Alzheimer’s.

He did, however, acknowledge that early-onset Alzheimer’s does have particularly strong genetic influences, all of which have not yet been discovered.

 — By Elizabeth Howell