Scientists have found a rare genetic mutation that appears to triple the risk for developing Alzheimer's disease and provides important clues into how the so-far incurable disease operates.
Scientists from two independent teams stumbled on the same result, published in two studies Wednesday in the New England Journal of Medicine: a mutation in the TREM2 gene, which helps govern immune system responses, is three to four times more common among elderly patients with Alzheimer's than those without the diagnosis.
The hallmark of Alzheimer's disease is the accumulation of plaques and tangles in the brain tissue. In normal bodies, it seems the immune system's inflammatory molecules help clear that build-up before it becomes a problem.
The TREM2 gene functions to keep that inflammatory response in check, to stop the inflammatory molecules from harming healthy tissue.
But preliminary research indicates the mutation could send the TREM2 gene into overdrive, hindering the inflammatory molecules from doing their job at all.
"While the genetic mutation we found is extremely rare, its effect on the immune system is a strong indicator that this system may be a key player in the disease," said University College London's Rita Guerreiro, lead author of one of the two studies.
The mutation is found in fewer than one in 200 people, and in fewer than one in 50 Alzheimer's patients, which means the mutation alone is unlikely to be enough to cause the disease.
A combination of environmental and hereditary factors are believed to contribute to developing Alzheimer's.
However, researchers said identifying this gene and its possible role in Alzheimer's is a step in the right direction.
"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," said Peter St. George-Hyslop, of the University of Toronto.
Another of the lead researchers, Kevin Morgan of the University of Nottingham, said "the risk associated with this new variant is the largest seen to date and heralds the start of a new era in (Alzheimer's Disease) 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."
The scientists said that new drugs could potentially be developed to target the TREM2 gene and stop it from overly interfering in the inflammatory response.
One of the studies was done by an international research team based in Britain, Canada and the US, using a data bank of 25,000 people.
The other was done by researchers in Iceland, using data from 2,261 elderly Icelanders and then confirmed with population samples in the US, Norway, the Netherlands and Germany.