In those with Alzheimer’s disease, the brain typically becomes clogged up with ‘plaques’ and ‘tangles’. Research has increasingly suggested that the immune system plays a role in this process, but it was not clear how. Now, a new study has revealed specific changes which take place in the immune system in the early stages of the disease – a significant revelation which could eventually lead to a whole new treatment strategy.
Researchers at Duke University used a breed of Alzheimer’s mice, genetically engineered to have a somewhat human-like immune system, to investigate immune changes in the early stages of the disease. They found that in Alzheimer’s disease, certain immune cells which normally protect the brain begin to abnormally consume an important nutrient – arginine.
Equipped with this information, they then used a small-molecule drug, called difluoromethylornithine (DFMO), to block this harmful process in the mice before the onset of Alzheimer’s. The drug was successful in preventing arginine consumption, and preventing the brain plaques and memory loss which are characteristic of Alzheimer’s disease.
“We see this study opening the doors to thinking about Alzheimer’s in a completely different way, to break the stalemate of ideas in Alzheimer’s disease,” says Carol Colton, professor of neurology at Duke University, and senior author of the new study. “The field has been driven by amyloid for the past 15, 20 years and we have to look at other things because we still do not understand the mechanism of the disease or how to develop effective therapeutics.”
The Next Step
While this study is a step towards better understanding Alzheimer’s and how it should be treated, there is still a lot more work to be done before the cause of the disease can be fully understood and an effective treatment administered to humans.
“Clinical trials are essential before any potential new treatment can be given to people, but these early findings could open new doors for future treatment development for Alzheimer’s” says Dr Laura Phipps, of Alzheimer’s Research UK. “The study suggests that low levels of arginine in the brain could contribute to the death of nerve cells in Alzheimer’s, but there is much more we still need to understand about how and why nerve cells die in the disease.”
Dr James Picket, head of research at the Alzheimer’s Society, says: “Importantly, these new findings reflect earlier observations that arginine is reduced in the brains of people with Alzheimer’s disease. The next step would be to show that targeting arginine metabolism in the brain can reduce the death of brain cells, as this was not shown in the current study.”
Now that they have seen the results of DFMO in mice when administered before the onset of Alzheimer’s symptoms, Colton’s team plan to test its effects when used after the symptoms appear.