Sugar coating for brain health
Carbohydrate-rich meshwork that covers cells could be key to understanding dementia
Changes in the complex chains of sugars that cover certain cells could be key to understanding cognitive decline and diseases including Alzheimer’s, Stanford Medicine researchers said. Neuroscientists have long focused on proteins and DNA as the likely culprits in dementia — not on sugars.
“This is like landing on a new planet,” said Nobel laureate Carolyn Bertozzi, PhD, professor of chemistry and the Baker Family Director of Sarafan ChEM-H. “We’re stepping outside for the first time and trying to make sense of what’s out there.”
In a study in aging mice, graduate student Sophia Shi, PhD, a former Stanford Bio-X fellow, uncovered striking age-related changes in the sugary coating — called the glycocalyx — on cells that form the blood-brain barrier, a membrane that protects the brain by filtering out harmful substances while allowing in essential nutrients.
“This work lays the foundation for a new field of inquiry into how the aging brain loses its resilience,” said Tony Wyss-Coray, PhD, the D.H. Chen Professor II, a professor of neurology and director of the Knight Initiative for Brain Resilience.
The study, published Feb. 26, 2025, in Nature, was jointly supervised by Bertozzi and Wyss-Coray. Shi is the lead author.
Wyss-Coray’s lab has extensively studied how aging impacts the blood-brain barrier, But Shi’s project was the first to investigate how age affects its sugary armor. The results were striking: In older mice, bottlebrush-shaped, sugar-coated proteins called mucins, a key component of the glycocalyx, were sharply reduced. This thinning of the glycocalyx correlated with increased blood-brain barrier permeability and heightened neuroinflammation.
When the team reintroduced the critical mucins in aged mice, restoring a more “youthful” glycocalyx, their blood-brain barrier integrity, neuroinflammation and cognitive function all improved.
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