A link has been established between Alzheimer''s disease (AD) and a rare gene mutation that affects the immune system''s inflammation response.
The discovery supports an emerging theory about the role of the immune system in the development of AD as a rare mutation in a gene called triggering receptor expressed on myeloid cells 2 (TREM2) that helps activate immune system responses, and raises the risk for developing the disease.
A study led by scientists at University College London (UK) used data on a total of 25,000 people. After homing in on the TREM2 gene using new sequencing techniques, they carried out further sequencing that identified a set of rare mutations that occurred more often in 1,092 Alzheimer''s disease patients than in a group of 1,107 healthy controls. With further follow-up studies involving a large number of Alzheimer''s disease patients and controls, they evaluated the most common mutation known as R47H, and confirmed that this variant of TREM2 substantially increases the risk for Alzheimer''s disease.
In a separate study, a team led by deCODE Genetics (Reykjavik, Iceland) involved collaborators from Iceland, Holland, Germany, and the USA. It too found a strong link between the R47H variant and AD, and, in addition, discovered the variant also predicts poorer cognitive function in older people without Alzheimer''s. The company''s genome sequencing and genotyping technology identified approximately 41 million markers, including 191,777 functional variants, from 2,261 Icelandic samples.
Kari Stefansson, MD, PhD, CEO and cofounder of deCODE Genetics, said "The discovery of variant TREM2 is important because it confers high risk for Alzheimer''s and because the gene''s normal biological function has been shown to reduce immune response that may contribute to the disease." Both studies were published on November 14, 2012, in the New England Journal of Medicine (NEJM).