Scientists from the University of Illinois Chicago have uncovered why our brain’s “protective filter” — the blood–brain barrier — becomes less effective with age, allowing unwanted substances to pass through and potentially leading to memory decline. The study, published in Cell Reports, opens new possibilities for the early treatment of age-related memory problems.

The blood–brain barrier is a layer of cells lining the brain’s blood vessels. It blocks viruses, bacteria, and toxins from entering, while letting in essential nutrients. A key role in its function is played by so-called tight junctions between cells, with one of the main “guards” in this system being the protein occludin.

As we age, the barrier begins to “leak,” which can cause memory problems as early as middle age. Until now, the mechanism behind this process was unclear.

In earlier experiments, the team led by Olga Komarova found that removing the protein N-cadherin from blood vessel cells makes the vessels more permeable — including in the brain. In the new study, the scientists investigated how this affects memory. They found that mice lacking functional N-cadherin retained memories more poorly: they learned normally but forgot quickly.

Brain analysis revealed that the culprit was again occludin. Without N-cadherin, its levels dropped, tight junctions weakened, and the barrier became more “porous.” The researchers discovered that when N-cadherins from neighboring cells connect, they trigger a signaling cascade that stabilizes occludin and maintains barrier integrity.

To check if the same occurs in humans, the team examined brain tissue samples collected during epilepsy surgeries. In middle-aged individuals, levels of both N-cadherin and occludin were lower than in young people — exactly as seen in mice.

This is the first study to show how N-cadherin–triggered signaling controls the tight junctions of the brain barrier. And since these changes begin as early as middle age, the scientists believe that age-related memory problems could be treated long before they become severe. The team is now searching for parts of this signaling pathway that can be targeted with drugs.