February 26, 2015
Researchers are discovering new ways in which inflammation and the immune system influence the progression of Alzheimer’s, offering new hope for one day finding effective treatments for the mind-robbing illness. But the findings also highlight how much scientists still don’t know about the disease and underscore the need for continuing research and funding into the ways that Alzheimer’s damages the brain, and how therapies might prevent that damage.
In two new studies, scientists looked at a substance called interleukin-10, or IL-10, one of many proteins that play a role in the body’s immune response to germs and injury. Specifically, IL-10 is known to play a critical role in inflammation, which is increasingly recognized as a contributing factor to heart disease, Alzheimer’s and other chronic diseases of aging.
IL-10 is traditionally thought of as an anti-inflammatory protein. But as these studies found, its activity may actually increase the buildup of beta-amyloid plaque, the sticky protein that forms microscopic clumps in the brains of those with Alzheimer’s. Both studies, published in the scientific journal Neuron, were conducted in mice that had been genetically engineered to develop a disease that resembles Alzheimer’s in people.
“Alzheimer’s disease is the public health crisis of our time, and effective treatment does not yet exist,” said Terrence Town, a professor of physiology and biophysics at the Keck School of Medicine at the University of Southern California and the senior author of one of the studies. “Our study shows that ‘rebalancing’ the immune response to wipe away toxic plaques from the brain may bring new hope for a safe and effective treatment for this devastating illness of the mind.”
In that study, Dr. Town and his colleagues blocked the activity of IL-10 and showed that the animals’ immune systems were able to clear the brain of toxic beta-amyloid plaque. The mice performed better in various tests of learning and memory than mice that had not had the IL-10 treatments. The scientists hope to study various drugs that target IL-10 to see how it might affect the Alzheimer’s disease process.
In the second study, scientists at the University of Florida similarly showed that IL-10 may play an important role in the buildup of beta-amyloid plaque in the brain. Interleukin 10 appeared to increase levels of a protein called APOE, which is known to affect the risk of developing Alzheimer’s. People who carry a form of APOE called APOE-E4 tend to produce high levels of beta-amyloid plaque and are at increased risk of developing the disease.
The findings suggest that Alzheimer’s treatments might need to be tailored to patients, depending on which form of APOE they carry in their genes.
“About 15 to 17 percent of the population has the APOE-E4 allele, and about 50 percent of people with Alzheimer’s have it,” said Dr. Todd Golde, the director of the Center for Translational Research in Neurodegenerative Disease at the University of Florida and the paper’s lead author. “This study offers additional insight into how environmental influences interact with people’s underlying genotypes to alter their risk for diseases.”
“We know that people are exposed to various inflammatory or anti-inflammatory stimuli throughout their lives,” Dr. Golde continued. “Depending on what their genotype is, that exposure may in some cases protect them from Alzheimer’s, or, in other cases, increase their risk for Alzheimer’s.”
Much more research is needed to elucidate the roles of IL-10 and inflammation in the development of Alzheimer’s disease. The researchers plan to carry out additional studies to examine how IL-10 affects plaque buildup in animals carrying different forms of the APOE gene. It will likely be many years before similar studies might be carried out in people.
Sources: Marie-Victoire Guillot-Sestier, Kevin R. Doty, David Gate, et al: “IL-10 Deficiency Rebalances Innate Immunity to Mitigate Alzhiemer-Like Pathology.” Neuron, Volume 85, Issue 3, Feb. 4, 2015
Paramita Chakrabarty, Andrew Li, Carolina Ceballos-Diaz, et al: “IL-10 Alters Immunoproteostasis in APP Mice, Increasing Plaque Burden and Worsening Cognitive Behavior.” Neuron, Vol. 85, Issue 3, Feb. 4, 201