Jacksonville (Florida) [USA] USA], The network of blood channels and tissues known as the blood-brain barrier, which nourishes and protects the brain from dangerous chemicals flowing in the blood, is compromised in Alzheimer's disease.
Mayo Clinic researchers and their partners have discovered distinct molecular markers of blood-brain barrier disruption, which may lead to new approaches to diagnosing and treating the condition.
In Nature Communications, his research is published.
"These signatures have high potential to become new biomarkers that capture brain changes in Alzheimer's disease," said senior author Nilufer Ertekin-Taner, MD, PhD, chair of the Department of Neuroscience at Mayo Clinic and leader of Genetics. Alzheimer's Disease and Endophenotypes. Mayo Clinic Laboratory in Florida.
To conduct the study, the research team analyzed human brain tissue from the Mayo Clinic Brain Bank, as well as published data sets and brain tissue samples from collaborating institutions. The study cohort included brain tissue samples from 12 patients with Alzheimer's disease and 12 healthy patients without confirmed Alzheimer's disease.
All participants had donated their tissues for science. Using these and external data sets, the team analyzed thousands of cells in more than six brain regions, making it one of the most rigorous studies of the blood-brain barrier in Alzheimer's disease to date, according to the researchers.
They focused on the brain's vascular cells, which make up a small portion of the brain's cell types, to examine the molecular changes associated with Alzheimer's disease. In particular, they looked at two types of cells that play an important role in maintaining the blood-brain barrier: pericytes, the brain's guardians that maintain the integrity of blood vessels, and their support cells known as astrocytes, to determine whether and as. they interact.
They found that samples from patients with Alzheimer's disease showed altered communication between these cells, mediated by a pair of molecules known as VEGFA, which stimulates blood vessel growth, and SMAD3, which plays a key role in cellular responses to external environment. Using cellular and zebrafish models, the researchers validated their finding that elevated levels of VEGFA lead to lower levels of SMAD3 in the brain.
The team used stem cells from blood and skin samples from donors with Alzheimer's disease and those in the control group. They treated the cells with VEGFA to see how it affected SMAD3 levels and overall vascular health. VEGFA treatment caused a decrease in SMAD3 levels in brain pericytes, indicating an interaction between these molecules.
According to the researchers, donors with higher levels of SMAD3 in their blood had less vascular damage and better outcomes related to Alzheimer's disease. The team says more research is needed to determine how SMAD3 levels in the brain impact SMAD3 levels in the blood.
Mayo Clinic researchers and their partners have discovered distinct molecular markers of blood-brain barrier disruption, which may lead to new approaches to diagnosing and treating the condition.
In Nature Communications, his research is published.
"These signatures have high potential to become new biomarkers that capture brain changes in Alzheimer's disease," said senior author Nilufer Ertekin-Taner, MD, PhD, chair of the Department of Neuroscience at Mayo Clinic and leader of Genetics. Alzheimer's Disease and Endophenotypes. Mayo Clinic Laboratory in Florida.
To conduct the study, the research team analyzed human brain tissue from the Mayo Clinic Brain Bank, as well as published data sets and brain tissue samples from collaborating institutions. The study cohort included brain tissue samples from 12 patients with Alzheimer's disease and 12 healthy patients without confirmed Alzheimer's disease.
All participants had donated their tissues for science. Using these and external data sets, the team analyzed thousands of cells in more than six brain regions, making it one of the most rigorous studies of the blood-brain barrier in Alzheimer's disease to date, according to the researchers.
They focused on the brain's vascular cells, which make up a small portion of the brain's cell types, to examine the molecular changes associated with Alzheimer's disease. In particular, they looked at two types of cells that play an important role in maintaining the blood-brain barrier: pericytes, the brain's guardians that maintain the integrity of blood vessels, and their support cells known as astrocytes, to determine whether and as. they interact.
They found that samples from patients with Alzheimer's disease showed altered communication between these cells, mediated by a pair of molecules known as VEGFA, which stimulates blood vessel growth, and SMAD3, which plays a key role in cellular responses to external environment. Using cellular and zebrafish models, the researchers validated their finding that elevated levels of VEGFA lead to lower levels of SMAD3 in the brain.
The team used stem cells from blood and skin samples from donors with Alzheimer's disease and those in the control group. They treated the cells with VEGFA to see how it affected SMAD3 levels and overall vascular health. VEGFA treatment caused a decrease in SMAD3 levels in brain pericytes, indicating an interaction between these molecules.
According to the researchers, donors with higher levels of SMAD3 in their blood had less vascular damage and better outcomes related to Alzheimer's disease. The team says more research is needed to determine how SMAD3 levels in the brain impact SMAD3 levels in the blood.
