A single genetic mutation increases the risk of developing Alzheimer's disease by threefold, say scientists from two independent research groups. The mutation occurs in the gene, TREM2, which is involved in the immune system, specifically in clearing up cell and protein debris.
'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', says lead author Dr Kari Stefánsson, CEO of deCODE Genetics, Iceland where one of the studies was carried out.
Genetic variants for the risk of developing the neurological disease, late-onset Alzheimer's, have previously been identified. However these variants have generally been associated with very low risk. Researchers at University College London and deCODE Genetics analysed the genomes of over 25,000 people and showed variations in the TREM2 gene increase the risk of developing Alzheimer's disease substantially.
Researchers found a specific mutation in TREM2, called R47H, occurred four times as often in patients with Alzheimer's compared to controls who did not have the disease. Although this mutation was found to be very rare, occurring in only 0.3 percent of the total population, it was shown to increase the likelihood of developing Alzheimer's disease by threefold.
Dr Rita Guerreiro who led the study at University College London said: 'These findings are particularly exciting because they give us a clear signal about what could be going wrong in Alzheimer's disease. While this genetic mutation is very rare its effect on the immune system is a strong indicator that this system may be a key player in the disease'.
In Alzheimer's, the protein beta-amyloid accumulates in plaques in the brain, causing brain cells to die. The mutation in TREM2 is suggested to reduce the ability of immune cells in the brain to remove these plaques.
'This is a landmark finding and reveals important new clues about the genetic causes of Alzheimer's disease', said Dr Eric Karran, director of Alzheimer's UK that part funded the study at University College London. 'For these findings to live up to their potential and make a difference to people's lives, it's crucial that research building on this work continues and the role of the immune system in Alzheimer's is fully explored'.
The studies were both published in the New England Journal of Medicine.