Certain immune cells that normally protect the brain abnormally consume the nutrient arginine in Alzheimer’s disease (AD) patients, suggests a study of mice with the cardinal features of AD.
The mice’s brain-resident immune cells called microglia express the immunosuppressive molecule CD11c on their surfaces and extracellular arginase accumulates in these same regions.
The researchers were able to pharmacologically prevent the mice from developing AD with the drug alpha-difluoromethylornithine (eflornithine). This drug blocked arginase, an enzyme that breaks down arginine, and significantly decreased the presence of CD11c expression. “Inhibition of abnormal arginine utilization resulted in a marked improvement in pathology and cognitive function,” they said.
“We suggest that immune suppression and arginine catabolism lead to a loss of arginine, a critical semiessential amino acid, and this nutrient deprivation is followed by cell death. This … may explain the temporal and spatial induction of the slow and persistent loss of neurons in humans with AD,” said Matthew J. Kan of Duke University and his colleagues.
Find the full study in the Journal of Neuroscience (doi:10.1523/JNEUROSCI.4668-14.2015).