Scientists Discover Brain Vascular Changes Associated with Alzheimer’s Disease
The blood-brain barrier (BBB)—a network of blood vessels and tissues that protects the brain from harmful substances in the blood—is disrupted in Alzheimer’s disease. Researchers at the Mayo Clinic and collaborators have now identified unique molecular signatures of BBB dysfunction, potentially leading to new diagnostic and treatment methods.
Discovery and Analysis of Molecular Signatures
“These signatures have high potential to become novel biomarkers that capture brain changes in Alzheimer’s disease,” says senior author Dr. Nilüfer Ertekin-Taner, chair of the Department of Neuroscience at Mayo Clinic and leader of the Genetics of Alzheimer’s Disease and Endophenotypes Laboratory at Mayo Clinic in Florida.
The study involved analyzing human brain tissue from the Mayo Clinic Brain Bank, published datasets, and samples from collaborating institutions. The cohort included brain tissue samples from 12 Alzheimer’s patients and 12 healthy controls, with all participants donating their tissue for research. “The team analyzed thousands of cells across more than six brain regions, making it one of the most rigorous studies of the BBB in Alzheimer’s disease to date.”
Furthermore, focusing on brain vascular cells, the researchers examined molecular changes linked to Alzheimer’s. Specifically, they studied pericytes and astrocytes, which are crucial for maintaining the BBB. They found altered communication between these cells in Alzheimer’s patients, mediated by VEGFA and SMAD3 molecules. Increased VEGFA levels led to decreased SMAD3 levels in the brain.
Validation and Future Research Directions
Using cellular and zebrafish models, the researchers confirmed that “higher VEGFA levels reduce SMAD3 in brain pericytes.” They treated stem cells from blood and skin samples of Alzheimer’s patients and controls with VEGFA, which led to decreased SMAD3 levels and improved overall vascular health. Higher blood SMAD3 levels correlated with reduced vascular damage and better outcomes in Alzheimer’s disease.
Additionally, future studies will examine the correlation between brain SMAD3 levels and blood SMAD3 levels. Moreover, they will investigate other molecules that play a role in preserving the integrity of the BBB in Alzheimer’s disease.
Read the Original Article on: Medical Xpress
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