Researchers successfully restore the brain's 'sweet layer' and recover memory

This sugar coat, known as the glycocalyx, sits on cells that form the blood-brain barrier. A recent study in mice found that the glycocalyx becomes thinner over time, leaving gaps that invite unwanted molecules to slip in.

“We’re stepping outside for the first time and trying to make sense of what’s out there,” said Carolyn Bertozzi, referencing how little attention sugar molecules have received compared to more commonly studied proteins.

The worry is that even minor openings can let inflammatory molecules and other damaging factors spread through the brain. Over the long run, that infiltration can potentially diminish memory and other cognitive abilities.

“This work lays the foundation for a new field of inquiry into how the aging brain loses its resilience,” said Tony Wyss-Coray, from Stanford University.

Brain tests of learning and recall showed that mice with replenished sugar layers performed better at certain memory tasks for the brain.

Open Access Paper published

Glycocalyx dysregulation impairs blood–brain barrier in ageing and disease

https://www.nature.com/articles/s41586-025-08589-9

The blood–brain barrier (BBB) is highly specialized to protect the brain from harmful circulating factors in the blood and maintain brain homeostasis1,2. The brain endothelial glycocalyx layer, a carbohydrate-rich meshwork composed primarily of proteoglycans, glycoproteins and glycolipids that coats the BBB lumen, is a key structural component of the BBB3,4. This layer forms the first interface between the blood and brain vasculature, yet little is known about its composition and roles in supporting BBB function in homeostatic and diseased states. Here we find that the brain endothelial glycocalyx is highly dysregulated during ageing and neurodegenerative disease. We identify significant perturbation in an underexplored class of densely O-glycosylated proteins known as mucin-domain glycoproteins. We demonstrate that ageing- and disease-associated aberrations in brain endothelial mucin-domain glycoproteins lead to dysregulated BBB function and, in severe cases, brain haemorrhaging in mice. Finally, we demonstrate that we can improve BBB function and reduce neuroinflammation and cognitive deficits in aged mice by restoring core 1 mucin-type O-glycans to the brain endothelium using adeno-associated viruses. Cumulatively, our findings provide a detailed compositional and structural mapping of the ageing brain endothelial glycocalyx layer and reveal important consequences of ageing- and disease-associated glycocalyx dysregulation on BBB integrity and brain health.

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What’s the overlap with the glycans in IgG? [sialyation for example?]

Ask the Point of Contact for the published paper.

https://www.nature.com/articles/s41586-025-08589-9

Tony Wyss-Coray

View ORCID ID profile

  • Stanford Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, Stanford, CA, USA

His email address is;

twc@stanford.edu

More importantly how do we apply this to human use now?

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Alex, I think you said you had access to the advanced ChatGPT model, why don’t you see what kind of response it gives you on this type of question?

Calroy Health sciences Arteriosil HP was designed to support and restore the endothelial glycocalyx. Whether it can reach the BB, I don’t know. Might be a good question to ask them.

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