Identifying an Alzheimer’s disease risk gene

2013

Challenge

Alzheimer’s disease is a devastating, progressive brain disease that affects as many as 5.1 million Americans, and is the most common cause of dementia among older people Alzheimer's Disease Fact Sheet. How the disease process begins remains unknown, creating an urgent need to better understand Alzheimer’s disease risks.

Advance

Two international teams of researchers, including IRP researchers led by Andrew Singleton, Ph.D., identified a unique variant in the TREM2 gene—a gene involved in inflammation and the immune response—as a significant risk factor for the development of late-onset Alzheimer’s disease.

Impact

For many years the only genetic variant consistently associated with late onset Alzheimer’s disease was in the ApoE4 gene. These are the first studies to identify the involvement of TREM2 in the Alzheimer’s disease process. TREM2 plays a very specific role within the immune system, which suggests that perturbation of this system in some way may lead to the development of the disease. Discovering that pathway now provides targets for potential therapies.

Publications

Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JS, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert JC, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St George-Hyslop P, Singleton A, Hardy J; Alzheimer Genetic Analysis Group. (2013). TREM2 Variants in Alzheimer’s Disease. N Engl J Med. 368(2), 117-27.