A new study from researchers at the University of Illinois Chicago reveals how the blood-brain barrier gets leakier with age, contributing to memory deficits. The study, published in Cell Reports [1], uncovered the molecular mechanisms behind this process and could provide new therapeutic targets to address cognitive decline earlier in the aging process.
The blood-brain barrier (BBB) is a highly selective semi-permeable barrier between the bloodstream and the brain's extracellular fluid.
The study is the first to look at how the signaling activated by N-cadherin controls organization of the tight junctions implicated in blood-brain barrier permeability, she said.
Because these deficits start to show in middle age, fairly early in the cognitive aging process, it’s not “too late in the game to start treatment,” said Komarova. Her team is now investigating if steps in the signaling pathway activated by N-cadherin could be therapeutic targets.
This paper shows that actually there might be a much bigger therapeutic window for treatment of any age-related cognitive decline condition.Yulia Komarova, UIC associate professor
It regulates the passage of molecules and ions, protecting the brain from harmful substances while allowing essential nutrients to enter. The BBB is crucial for maintaining a stable environment for proper brain function and preventing infections. A closer look at the brains of these mice showed that the issue was linked to a protein called occludin, which helps form tight junctions in the blood-brain barrier. Both aging brains and young brains lacking N-cadherin had fewer occluding junctions, resulting in a leakier barrier. Molecular experiments showed that when N-cadherin proteins on neighboring blood vessel cells interact, they trigger a signaling pathway that stabilizes occludin, helping to maintain the integrity of the blood-brain barrier.
Komarova collaborated with Dr. Jeffrey Loeb, head of neurology and rehabilitation in the College of Medicine, to examine human brain tissue from the university’s Neuro Repository collected during epilepsy surgeries. Comparing samples from younger patients (late teens to 20s) with those from middle-aged patients (40s to 50s), they found that the older group had reduced levels of both N-cadherin and occludin, mirroring the findings in mice. Its also evident from the previous findings that occludin and epithelial barriers have critical effect as a result of ageing on Blood-brain barrier.
Other UIC co-authors on the paper include Quinn Lee, Wang Ching Chan, Shuangping Zhao, Harry Hailemeskel, Riya Thomas, Mohsin Zafar, Fozia Mir, Peter Toth and Kamra.
Reference-
1) https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00602-3
(Newswise/CAG)