Alzheimer’s disease is the most common cause of dementia, slowly robbing millions of people around the world of their memory and independence.
For decades, scientists have known that the brain’s immune cells—called microglia—play an important but puzzling role in this disease. These tiny cells act like the brain’s clean-up crew, clearing out harmful waste and dead cells.
But under certain conditions, they can also become overactive, causing inflammation that damages the brain. Understanding how these cells switch between helping and harming has been one of the biggest mysteries in Alzheimer’s research.
Now, scientists from the Icahn School of Medicine at Mount Sinai, together with researchers from Germany’s Max Planck Institute for Biology of Ageing, The Rockefeller University, The City University of New York, and several other international institutions, have uncovered an important clue.
They discovered a special type of microglia that seems to protect the brain rather than harm it. The finding, published in the journal Nature, could open the door to new treatments that slow or even prevent Alzheimer’s disease.
In their study, the research team found that microglia with lower levels of a protein called PU.1 and higher levels of another molecule called CD28 were especially good at calming inflammation in the brain.
These protective cells also slowed the buildup of two harmful substances—amyloid plaques and tau proteins—that are known to cause the memory loss and brain damage seen in Alzheimer’s patients.
PU.1 is a transcription factor, which means it helps control which genes are turned on or off in a cell. CD28, on the other hand, is a receptor that usually appears on immune cells outside the brain, helping them communicate and stay active.
The discovery that CD28 also plays a role in brain cells came as a surprise and suggests that the immune system and the brain share more similarities than scientists once thought.
To study how these microglia work, researchers used mice that mimic Alzheimer’s disease as well as human brain cells and tissue samples. They found that when PU.1 levels were reduced, microglia began to behave more like other immune cells in the body.
Even though this special type of microglia made up only a small portion of all brain immune cells, their effect was widespread—they helped quiet brain inflammation and protected memory in the mice.
When scientists removed CD28 from these protective microglia, the opposite happened. Inflammation increased, and the buildup of harmful plaques became worse. This confirmed that CD28 plays a key role in keeping these microglia in their brain-protecting state.
Dr. Anne Schaefer, senior author of the study and a leading neuroscientist at Mount Sinai, explained that this discovery changes how we think about microglia. “They’re not just destructive responders in Alzheimer’s,” she said. “They can also act as protectors of the brain.”
Another scientist involved in the study, Dr. Alexander Tarakhovsky from The Rockefeller University, pointed out that the same molecules that control immune cells in the rest of the body are also guiding microglia in the brain. This could lead to new ways to treat Alzheimer’s by fine-tuning how the immune system interacts with the brain.
The findings also connect to previous genetic research by Dr. Alison Goate, a co-author of the paper. Her earlier studies found that people with naturally lower levels of PU.1—caused by a genetic variant—tend to have a lower risk of developing Alzheimer’s.
This new work helps explain why. It shows that lowering PU.1 encourages the creation of protective microglia that help prevent damage from Alzheimer’s-related proteins.
This discovery is exciting because it provides a new way to think about Alzheimer’s treatment. Instead of focusing only on removing amyloid plaques or tau tangles, future therapies could aim to strengthen these protective microglia or adjust PU.1 and CD28 activity.
In other words, we might be able to help the brain heal itself by training its immune cells to fight smarter, not harder.
The research was funded by several organizations, including the U.S. National Institutes of Health, the European Research Council, and the Alzheimer’s Association. Their support highlights the growing global effort to understand and stop Alzheimer’s disease.
In summary, this study adds an important piece to the Alzheimer’s puzzle. It shows that the brain’s immune system is not simply a source of inflammation—it’s also a potential source of protection.
By learning how to guide microglia toward their protective state, scientists may one day be able to prevent or slow Alzheimer’s before it steals more lives. This discovery not only changes our understanding of brain health but also gives hope for new, smarter therapies that work with the body’s own defenses.
If you care about Alzheimer’s disease, please read studies about the protective power of dietary antioxidants against Alzheimer’s, and eating habits linked to higher Alzheimer’s risk.
For more health information, please see recent studies that oral cannabis extract may help reduce Alzheimer’s symptoms, and Vitamin E may help prevent Parkinson’s disease.
The study is published in Nature.
Copyright © 2025 Knowridge Science Report. All rights reserved.
