Gene Discovered That Triples Risk Of Alzheimer's Disease
November 15, 2012

Gene Discovered That Triples Risk Of Alzheimer’s Disease

Connie K. Ho for — Your Universe Online

A group of researchers from 44 different institutions around the world, including scientists from the Mayo Clinic, the University of Toronto, and the University of Nottingham, recently discovered a gene that almost triples the risk of developing Alzheimer´s disease.

The international group of scientists utilized the Nottingham ARUK DNA bank, one of the biggest collections of DNA pooled from Alzheimer´s patients. The team of investigators were able to piece together the new set of findings with sequencing techniques that focused on the TREM2 gene, which later lead to the identification of a group of rare variations in TREM2 that was found more frequently in 1,092 Alzheimer´s disease patients as compared to the control group of 1,107 healthy individuals. The results of the study were recently published in the online edition of the New England Journal of Medicine.

"This discovery provides an increasingly firm link between brain inflammation and increased risk for Alzheimer's," noted Dr. Peter St George-Hyslop, director of the Tanz Centre for Research in Neurodegenerative Diseases at the University of Toronto, in a prepared statement. "This is an important step towards unraveling the hidden causes of this disease, so that we can develop treatments and interventions to end one of the 21st century's most significant health challenges."

In a group of follow-up studies, the researchers evaluated R47H, the most common variant. Physicians from the Mayo Clinic evaluated the patients and control group participants. Based on the findings, it was noted that the R47H variant in TREM2 elevated the risk of developing Alzheimer´s disease significantly.

"The TREM2 variant may be rare, but it is potent," explained Minerva Carrasquillo, a scientist with the Mayo Clinic, in a prepared statement. "In our series, it was present in 1.9 percent of the Alzheimer's patients and in only 0.37 percent of the controls. This strong effect rivals that of the well-established genetic variant known as APOE4, and it was observed both in our study and in the independent study led by deCODE that was published with ours. R47H isn't fully penetrant – meaning that not all people who have the variant will develop Alzheimer's and in those who do, other genes and environmental factors will also play a role – but like APOE4 it does substantially increase risk."

In particular, R47H is considered the first “goldilock” variant to have a strong correlation with Alzheimer´s disease. It is called “goldilock” as it is the variant that is “just right” — commonly identified in large populations, but so rare that it can refer researchers to a possible genetic mutation that could help in identifying risk factors for Alzheimer´s disease.

"The variant found in our study identifies a fascinating new Alzheimer's disease gene, TREM2, which is involved in the immune system," remarked Rosa Rademakers, a researcher at the Mayo Clinic, in the statement. "This fits well with other evidence linking the immune system to Alzheimer's disease, but additional studies are needed to establish that R47H does, in fact, act by altering immune function. Fortunately, this variant changes an amino acid in TREM2 and that will greatly facilitate the biological studies that follow."

The researchers believe that the study comes at an important junction in time as the cause of Alzheimer´s is still unclear. Scientists believe that the disease is due to a complex mix of environmental and genetic factors. In addition, new technology has allowed for more analysis of genes and study of rare mutations in genes.

"The risk associated with this new variant is the largest seen to date and heralds the start of a new era in AD genetic research. At long last we are beginning to witness major breakthroughs that will hopefully result in therapeutic developments to help alleviate this devastating condition,” remarked Kevin Morgan, a professor of human genomics and molecular genetics at the University of Nottingham, in a prepared statement.