Researchers at Mayo Clinic and their collaborators have discovered distinct molecular signatures of blood-brain barrier dysfunction in Alzheimer’s disease. This discovery could lead to new methods for diagnosing and treating the disease. The blood-brain barrier, which consists of blood vessels and tissues, is responsible for nourishing and shielding the brain from harmful substances in the bloodstream. However, it is compromised in individuals with Alzheimer’s disease.The molecular indicators of blood-brain barrier dysfunction may lead to new methods for diagnosing and treating the disease. The study’s results are detailed in the journal Nature Communications.
Dr. Nilüfer Ertekin-Taner, the chair of the Department of Neuroscience at Mayo Clinic, suggests that these indicators have the potential to be valuable biomarkers for tracking brain changes in Alzheimer’s disease.
The research team examined human brain tissue from Mayo Clinic’s Brain Bank to conduct their study.The study used brain tissue samples from 12 Alzheimer’s patients and 12 healthy patients, all of whom donated their tissue for science. The researchers analyzed thousands of cells in over six brain regions, making it one of the most comprehensive studies of the blood-brain barrier in Alzheimer’s disease to date. They specifically looked at brain vascular cells, which are a small portion of the brain’s cell types. The research also utilized data from the Genotype-Tissue Expression Project and brain tissue samples from other institutions.The researchers examined changes at the molecular level that are linked to Alzheimer’s disease. They focused on two types of cells that are crucial for maintaining the blood-brain barrier: pericytes, which are responsible for protecting the brain’s blood vessels, and their supporting cells called astrocytes. The goal was to understand if and how these cells interact with each other. Their findings showed that there is a communication breakdown between these cells in samples taken from Alzheimer’s disease patients. This breakdown is influenced by two molecules called VEGFA, which promotes blood vessel growth, and SMAD3, which is involved in how cells respond to their environment. The researchers used both cellular and molecular techniques to conduct their investigation.The researchers used zebrafish models to confirm their discovery that higher levels of VEGFA result in decreased levels of SMAD3 in the brain. They conducted experiments using stem cells from both Alzheimer’s disease patients and individuals in the control group, treating the cells with VEGFA to observe its impact on SMAD3 levels and overall vascular health. The VEGFA treatment was found to reduce SMAD3 levels in brain pericytes, indicating an interaction between these molecules. Additionally, the researchers noted that donors with higher blood SMAD3 levels experienced less vascular damage and better outcomes related to Alzheimer’s disease.More research is necessary to determine the relationship between SMAD3 levels in the brain and SMAD3 levels in the blood. The researchers intend to further investigate the SMAD3 molecule and its effects on vascular and neurodegenerative issues in Alzheimer’s disease. They also aim to identify other molecules that may be involved in maintaining the blood-brain barrier. This study is part of a federal grant that supports projects focused on identifying targets for the treatment of Alzheimer’s disease. The research received support from the National Institutes of Health, National Institute on Aging, the Alzheimer’s Association Zenith Fellows Award, and Mayo Clinic Center for Regenerative Bioth.Medical treatments.
