A New Potential Cause for Alzheimer’s: Arginine Deprivation
Alzheimer’s study suggests immune cells chew up an important amino acid
April 14, 2015
DURHAM, NC - Increasingly, evidence supports the idea that the immune system, which protects our bodies from foreign invaders, plays a part in Alzheimer’s disease. But the exact role of immunity in the disease is still a mystery.
A new Duke University study in mice suggests that in Alzheimer’s disease, certain immune cells that normally protect the brain begin to abnormally consume an important nutrient: arginine. Blocking this process with a small-molecule drug prevented the characteristic brain plaques and memory loss in a mouse model of the disease.
Published April 15 in the Journal of Neuroscience, the new research not only points to a new potential cause of Alzheimer’s but also may eventually lead to a new treatment strategy.
“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.
The brains of people with Alzheimer’s disease show two hallmarks -- ‘plaques’ and ‘tangles’ -- that researchers have puzzled over for some time. Plaques are the build up of sticky proteins called beta amyloid, and tangles are twisted strands of a protein called tau.
The group did find 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 small drug difluoromethylornithine (DFMO) before the start of symptoms in the mice, the scientists saw fewer CD11c microglia and plaques develop in their brains. These mice performed better on memory tests.
“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.
