In the battle against Alzheimer’s disease, inflammation may be an ally, not a foe, a new study has found.
Immune cells in the brain previously blamed for Alzheimer’s actually protect against the disease by corralling the damage-causing amyloid plaques, according to the Yale University study, published Wednesday in the journal Neuron.
The findings suggest that inflammation byproducts of these immune cells, known as microglia, probably don’t cause Alzheimer’s, nor are they as effective as previously believed at “gobbling up” the plaques, both of which have been hypothesized, said Jaime Grutzendler, associate professor of neurology and neuroscience and the study’s lead author. Rather, he said, the cells act as a physical barrier that encloses the spiky plaques, preventing outward expansion and making them less toxic.
“They’re sort of like garbage compactors,” he said. “They tightly surround the plaques and make them inert and less damaging … by creating a capsule.”
The study found that amyloid plaques were fluffier and spikier, and thus more harmful, in the brains of people with a genetic mutation that prevents the microglia from surrounding them. People with the mutation are about 10 times as likely to develop Alzheimer’s than the general population.
The finding may help scientists understand why some people with the plaques develop the cognitive degeneration associated with the disease while others never do.
“It’s always been a mystery,” Grutzendler said. “Why do people who don’t have a lot of plaques get Alzheimer’s disease and other people who have a lot of plaques don’t?”
The answer may be that even among some people who don’t have the mutation, the microglia may lose their function over time, while other people’s microglia continue to corral the plaques, he said. Whether a person develops symptoms may be a matter of balance, between “how many plaques you have and how contained they might be.”
Richard Caselli, a professor of neurology at the Mayo Clinic and clinical core director for the Alzheimer’s Disease Center in Arizona, called the study groundbreaking. “It’s cool; it’s putting us in the opposite direction of what some of the common wisdom has assumed,” he said.”It excites me, because all the old directions have been failing miserably.”
There is no treatment for Alzheimer’s. But the study suggests that efforts should probably be made to enhance the immune cells’ function rather than suppress it, Grutzendler said. “People have tried to do these treatments in the past to reduce inflammation, and it hasn’t worked,” he said. “We think these cells probably need to be left alone.”
Heather Snyder, senior director of medical and scientific operations at the Alzheimer’s Association, praised the study and said it would further understanding of the relationship between microglia and the plaques - a relationship in which timing may play an important role.
“There may be a window of time where this activity or behavior is positive, and there may be a window of time where this activity or behavior is negative. Timing it and being able to detect those changes is key,” she said.
Once the relationship is better understood, she said, “the next step would be to think about being able to target the immune system as a potential therapy and moving it into early clinical trials.”
About the Author
