Scientists have long known that disruptions of the blood-brain barrier in the brain contribute to the development of neurodegeneration, but the specific contribution of endothelial cells lining blood vessels to this mechanism has remained unclear. The main challenge until now has been the difficulty of isolating these cells from tissue for further study. Therefore, scientists have developed an innovative approach to enriching these cells from frozen tissue. The findings of the study were published on the University of Connecticut website.
The application of the new technology led to an unexpected discovery: endothelial cells from three different neurodegenerative diseases (Alzheimer's disease, amyotrophic lateral sclerosis, and frontotemporal dementia) had fundamental similarities that distinguished them from endothelium in healthy aging.
The key change was the depletion of the RNA-binding protein TDP-43. From previous studies, the scientists knew of a genetic link between TDP-43 and the three diagnoses under study. However, while observations had previously focused primarily on neurons, dysfunction in endothelial cells is now evident.
"It's easy to think of blood vessels as passive conduits, but our results challenge this notion. We now know that vascular changes are not collateral damage—they actively contribute to disease progression," concluded study author Omar Mustafa Fathi. In future studies, the scientists will target the cardiovascular system for the prevention and early detection of neurodegeneration.
Previously, scientists obtained supporting data in another study. It was established that poor vascular health accelerates brain aging.
