Alzheimer's breakthrough could "reverse the disease"
15 Apr 2015
A study conducted by researchers at Duke University, US points not only to a potential new cause of Alzheimer’s disease, but also to the possibility of a new treatment strategy.
Using genetically modified mice, the Duke University research team found that in Alzheimer’s disease, certain microglia immune cells that normally protect the brain begin to abnormally consume an important nutrient - arginine.
According to the researchers, blocking this process with a small-molecule drug prevented the characteristic brain plaques and memory loss in a mouse model of the disease.
“If indeed arginine consumption is so important to the disease process, maybe we could block it and reverse the disease
Study author Carol Colton
Alzheimer’s disease is the most common type of dementia, affecting almost 500,000 people in the UK, NHS figures suggest.
“If indeed arginine consumption is so important to the disease process, maybe we could block it and reverse the disease,” said senior author Carol Colton, professor of neurology at the Duke University School of Medicine, and a member of the Duke Institute for Brain Sciences.
Looking at the gradual onset of disease within the genetically modified mouse gave researchers a chance to study its brain over time and to focus on how the disease begins, said the study’s first author Matthew Kan.
The research group found that CD11c microglia and arginase, an enzyme that breaks down arginine, are highly expressed in regions of the brain involved in memory, in the same regions where neurons had died.
Blocking arginase using the cancer treating drug difluoromethylornithine (DFMO) before the start of symptoms in the mice, the scientists saw fewer CD11c microglia and plaques develop in their brains.
“All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect - the mouse, at least - from Alzheimer’s disease,” Kan said.
However, Colton said that the study does not suggest people should consume more arginine to help combat the 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,” Colton said.
“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 disease or how to develop effective therapeutics,” she said.
Experts have welcomed the research but have been quick to echo Colton’s patience, calling on the need for further investigation.
“The research is in mice, so it will be important to build on the findings with further studies in humans,” said Laura Phipps, Alzheimer’s Research UK science communications manager.
“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.”
A full account of the study has been published in the Journal of Neuroscience.
