Alzheimer’s disease is projected to affect 15 million people by mid-century if no cure or prevention is found. Now, a new study in mice offers hope that we are on track to better understanding, and possibly preventing, the disease.
The study, published in the Journal of Clinical Investigation, showed that the poor performance of brain cells known as microglia may explain why nerve cells in the brain die in patients with Alzheimer’s. The study also showed that blocking a single molecule on the surface of microglia could reverse memory loss.
How Microglia Work
Dr. Katrin Andreasson, a professor of neurology and neurological sciences at the Stanford University School of Medicine and senior author of the study, told Healthline that microglia are immune cells in the brain.
“[Microglia] are responsible for maintaining a healthy environment, getting rid of viruses, bacteria, and proteins that accumulate and can cause injury, like amyloid, which accumulates in the brain in Alzheimer's disease,” Andreasson said.
About 10 to 15 percent of all brain cells are microglia. Microglia patrol the brain and recruit other microglia if trouble is found. They consume invading bacteria and viruses to protect the brain and help to reduce inflammation.
On the other side of the spectrum is a protein called amyloid-beta, which is known for forming plaques. Amyloid-beta is produced throughout the body and becomes toxic to nerve cells when clumped into clusters. This protein is thought to play an important role in causing Alzheimer’s disease.
From Petri Dish to Disease Prevention?
Because isolating microglia from the brain can be challenging, Andreasson and her team harvested large amounts of their close cousins: immune cells called macrophages. Macrophages circulate in the body and can be collected with a blood sample. Although not identical, macrophages and microglia share a number of genetic, biochemical, and behavioral features.
For the study, the researchers placed macrophages from mice in a dish with amyloid-beta clusters. Macrophages from young mice produced recruiting chemicals without an increase in inflammatory molecules. They also made many enzymes that could digest amyloid-beta.
But in macrophages from older mice, amyloid-beta caused a large activity increase in EP2, a protein on the surface of microglia. This led to an increase in inflammatory molecules and a reduction in recruiting chemicals and amyloid-beta digesting enzymes.
“With aging, but especially with Alzheimer's, the microglia become less and less effective at doing their job,” Andreasson said. “So the brain environment becomes more toxic. There’s a lot more inflammation, which is not good for neurons, and there’s a lot more amyloid accumulating, which also injures neurons.”
By blocking EP2 in both groups of mice, researchers saw a significant improvement in two kinds of memory tests. One test evaluated how quickly a mouse forgot an object it had seen before. The other tested how well a mouse remembered where a food reward was in a maze.