Dr. Hugh Delaney spent years studying the tiny immune cells that live inside everyone's brain. Most scientists believed these cells, called microglia, only made Alzheimer's disease worse by causing inflammation. But Delaney, a Ph.D. student at Trinity College Dublin in Ireland, discovered something surprising: microglia actually help keep brain circuits stable and working properly.
Delaney's research, published in the scientific journal Brain, found that when researchers used a drug to reduce microglia activity in mice with Alzheimer's-like disease, the results were the opposite of what they expected. The mice's brains became more electrically unstable, not better. They experienced more seizure-like events, not fewer. The study challenges a common assumption about how Alzheimer's works and could change how scientists think about treatment development.
More than 55 million people worldwide live with Alzheimer's disease, which is the leading cause of dementia. While memory loss is the symptom most people know about, scientists have increasingly recognized that the disease also disrupts how neurons—the brain's wiring—communicate with each other. Some of these disruptions look similar to what's seen in epilepsy.
The Dublin team treated mice with a drug that blocks a receptor called CSF1R. This receptor is currently being studied as a target for experimental neurodegenerative disease treatments. Reducing microglia did partially protect the connections between neurons. But it also increased abnormal electrical activity in the brain and made seizure-like events worse. The treatment did not improve memory performance either.
"We expected that reducing microglial activation might improve the function of brain networks affected by Alzheimer's disease," said Professor Mark Cunningham, a physiology professor at Trinity's School of Medicine who co-led the study. "Instead, we found the opposite."
Professor Colm Cunningham, a neuroscience professor at Trinity's School of Biochemistry and Immunology and the study's other senior author, put it this way: "Microglia have often been viewed as drivers of harmful inflammation in Alzheimer's disease. Our findings indicate that the story is more complex."
The researchers now believe microglia perform important "housekeeping" functions in the brain. They help remove problematic connections between neurons and keep electrical activity under control. Interfering with these functions, even with good intentions, could cause unintended harm.
The findings don't mean microglia should never be targeted by treatments. Instead, the scientists suggest future therapies will need to be more selective—blocking the harmful inflammatory processes while preserving the beneficial housekeeping work these cells do.
The study also strengthens growing evidence that abnormal brain electrical activity is an important feature of Alzheimer's that deserves more attention from researchers developing new treatments.