A breakthrough study has identified a class of natural gene variants that may protect against Alzheimer's disease.
For the study, researchers at University College London analyzed DNA from more than 10,000 people — half with Alzheimer's and half without. The investigators found that these gene variants reduce the functioning of proteins called tyrosine phosphatases.
These proteins impair the activity of a cell signaling pathway important for cell survival, explained the authors of the study published online Feb. 5 in the Annals of Human Genetics.
The pathway could be a key target for drugs to treat Alzheimer's, and the study authors said that the findings provide more evidence that other genes may be linked to one's risk for the memory disorder.
"These results are quite encouraging. It looks as though when naturally occurring genetic variants reduce the activity of tyrosine phosphatases, then this makes Alzheimer's disease less likely to develop, suggesting that drugs which have the same effect might also be protective," lead author David Curtis said in a college news release. He's a professor of genetics, evolution and environment.
Previous research in mice and rats suggested that inhibiting the function of these proteins might help protect against Alzheimer's, but this study is the first to find such an effect in people.
There are already drugs that target tyrosine phosphatases, but they haven't been tested in human clinical trials, Curtis noted.
"Here's a natural experiment in people that helps us understand how Alzheimer's disease develops: as some people have these genetic variants and some don't, we can see that the impact of having particular variants is a reduced likelihood of developing Alzheimer's disease," he said.
Evidence also suggests that genetic variants that damage the gene for the PI3K protein are associated with an increased risk of Alzheimer's.
"There is a consistent story in our results that the activity of the … signaling pathway is protective, which is exactly in line with findings from animal studies," Curtis said.