When people talk about brain diseases like Alzheimer’s or stroke, they usually think about neurons—the brain cells responsible for thinking, memory, and movement.
But new research shows that other brain cells may play a bigger role than we once thought.
A team of scientists from Gladstone Institutes and UC San Francisco (UCSF) has found that many of the genes linked to brain diseases actually work in the brain’s border cells—those that form the blood-brain barrier.
These include blood vessel cells and immune cells that help protect the brain from harmful substances. The study was published in the journal Neuron.
“We hope this discovery gets people to pay more attention to the cells that guard the brain,” said Dr. Andrew Yang, the senior author. “They might be the key players in diseases like Alzheimer’s.”
The blood-brain barrier acts like a security system for the brain. It controls what gets in and out, removes waste, and blocks harmful invaders. But until now, researchers didn’t know exactly how many of the genetic risk factors for brain diseases affect these important cells.
Over the years, scientists have identified many DNA changes that increase a person’s risk for diseases like Alzheimer’s and stroke. But most of these changes don’t lie within actual genes—they’re in nearby regions once thought to be “junk DNA.” These areas act like dimmer switches, controlling when and how strongly a gene is turned on.
To figure out which cells these switches affect, the Gladstone team built a new tool called MultiVINE-seq. It allowed them to isolate and study the blood vessel and immune cells in donated human brain tissue. They examined both healthy and diseased brains.
Using this tool, they mapped gene activity and the dimmer switch settings in individual cells. They then matched these findings with genetic data from thousands of people with Alzheimer’s, stroke, and other brain conditions.
What they found was surprising: many of the risk-related switches were most active in blood vessel and immune cells—not in neurons.
Each disease affected the brain’s border cells differently. In stroke, the damaging changes were linked to weaker blood vessel structure. In Alzheimer’s, the changes activated immune cells too strongly, leading to inflammation.
One common DNA variant linked to Alzheimer’s affects a gene called PTK2B, especially in T cells (a type of immune cell). This variant is found in about one-third of people and may cause the immune system to go into overdrive near the brain’s toxic amyloid plaques.
Interestingly, PTK2B is already being targeted in cancer drug trials, raising the exciting possibility that these drugs could also help with Alzheimer’s.
Because the brain’s guardian cells sit at the border between the brain and body, they’re influenced by things like diet, exercise, and pollution.
This means that lifestyle changes might help protect these cells and lower disease risk. Also, because these cells are on the outside, they may be easier to treat with drugs that don’t need to cross the blood-brain barrier.
“This research shifts the focus to the brain’s gatekeepers,” said Yang. “They may hold the key to protecting the brain—and stopping diseases—before they start.”
If you care about Alzheimer’s disease, please read studies about Scientists find a new way to treat Alzheimer’s disease and findings of Fluctuating cholesterol and triglyceride levels are linked to Alzheimer’s disease.
For more about Alzheimer’s disease, please read studies about Scientists find root cause of tau tangles in Alzheimer’s disease and findings of new treatment for early-onset Alzheimer’s disease.
The study is published in Neuron.
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