Stanford researchers have identified changes in the brain’s glycocalyx, a sugar coating on cells, as potentially key to understanding cognitive decline and diseases such as Alzheimer’s. The study, led by Sophia Shi, a Stanford Bio-X Graduate Fellow, highlights how age-related changes in this sugary armor weaken the blood-brain barrier. This degradation allows harmful molecules to infiltrate the brain, possibly leading to inflammation and neurodegenerative diseases.
Nobel laureate Carolyn Bertozzi and neuroscientist Tony Wyss-Coray supervised the research. Bertozzi stated, “This is like landing on a new planet,” while Wyss-Coray emphasized that the work “lays the foundation for a new field of inquiry into how the aging brain loses its resilience.”
The study revealed that in older mice, mucins—sugar-coated proteins crucial to the glycocalyx—were significantly reduced. Restoring these mucins improved blood-brain barrier integrity and cognitive function. Shi remarked on the potential therapeutic implications: “Modulating glycans has a major effect on the brain – both negatively in aging when these sugars are lost, and positively when they are restored.”
Bertozzi noted that traditional views may underestimate sugars’ roles in biological processes: “Biology is often about looking in the right place.” She added that sugars might play an active role in brain aging.
Shi plans to continue exploring glycans’ roles at Harvard’s Rowland Institute. Her work opens possibilities for tackling neurodegenerative diseases like Alzheimer’s by identifying molecular pathways behind glycocalyx changes.
Stanford’s Office of Technology Licensing has filed for a patent related to this study. Other contributors include researchers from various institutions such as Picower Institute for Learning and Memory and Hong Kong Center for Neurodegenerative Diseases.
Funding came from multiple sources including the Department of Veterans Affairs and National Institutes of Health.
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