Scientists Discover Brain Cells That Could Help Stop Alzheimer’s

Researchers at Mount Sinai and international partners have identified special immune cells in the brain that seem to slow down Alzheimer’s disease, the researchers reported Saturday. These cells reduce inflammation and stop harmful proteins from spreading, protecting memory and brain health. Scientists say this could open the door to new treatments that strengthen the brain’s natural defenses.

Alzheimer’s disease, the leading cause of dementia, involves complex changes in the brain. Microglia—the immune cells that act as the brain’s cleanup crew—can either protect against damage or make it worse, depending on how they function. Understanding how these cells behave is key to figuring out how Alzheimer’s develops.

The research team from the Icahn School of Medicine at Mount Sinai, along with scientists from Germany, Rockefeller University, and other institutions, found a unique type of microglia that only protects the brain, and influences other microglia to do the same. This microglia has a lowered level of a protein called PU.1, and a higher level of a receptor called CD28. Their findings, published in Nature, could lead to new therapies that prevent or delay Alzheimer’s.

These cells also slow the buildup of amyloid plaques and “toxic tau” proteins; two major signs of Alzheimer’s.

Using lab mice and human brain samples, scientists showed that lowering PU.1 encouraged microglia to take on protective roles. Although these microglia are only a small fraction of all brain immune cells, they had a large impact, reducing inflammation and helping preserve memory in the mice.

When the researchers removed CD28 from these protective microglia, inflammation worsened and more plaques appeared, confirming CD28’s critical role.

“Microglia are not simply destructive responders in Alzheimer’s disease—they can become the brain’s protectors,” Anne Schaefer, MD, PhD, senior author of the study told Science Daily. “This finding extends our earlier observations on the remarkable plasticity of microglia states and their important roles in diverse brain functions. It also underscores the vital importance of international collaboration in advancing scientific progress.”

The study builds on earlier genetic work by Dr. Alison Goate of Mount Sinai, who found that people with a specific variant in the SPI1 gene—which controls PU.1—have a lower risk of Alzheimer’s. “These results provide a mechanistic explanation for why lower PU.1 levels are linked to reduced Alzheimer’s disease risk,” said Dr. Goate.

Overall, the discovery of how PU.1 and CD28 work together gives researchers a new understanding of how to harness the brain’s immune system to fight Alzheimer’s. It also supports the growing idea that targeting microglial activity could be a promising approach for new treatments.

The study was supported by the National Institutes of Health, the European Research Council, the Alzheimer’s Association, and other organizations dedicated to advancing research on neurodegenerative diseases.