2023 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)
Towards The Molecular Map of Blood Vessels in Health and Neurodegeneration
Could new biological markers increase understanding of brain blood vessel function in Alzheimer’s?
Ricardo Giordano, Ph.D.
University of Sao Paulo (Universidade de São Paulo), USP
São Paulo, Brazil
Background
The blood-brain barrier (BBB) is a specialized structure that helps maintain a healthy brain environment by tightly regulating what goes into and out of the brain from the circulating blood. The BBB is composed of different kinds of cells that help clear toxic debris from the brain. Normal functioning of the BBB is essential to protect the brain from harmful changes. Problems with the BBB are often associated with brain disorders such as Alzheimer’s. The BBB can make it difficult to study and treat these disorders since it limits access to brain blood vessels.
Dr. Ricardo Giordano and colleagues have developed a technique to identify biological markers, or “biomarkers,” for brain blood vessels. They have characterized a biomarker located on brain blood vessels that can distinguish the BBB from other blood vessels near the brain. Additional biomarkers with this level of specificity could help researchers better understand the molecular mechanisms behind brain blood vessel function in Alzheimer’s.
Research Plan
Dr. Giordano’s team will search for additional biomarkers specific to BBB changes that occur during brain disorders using genetically engineered mouse models of Alzheimer’s and amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease).
First, the researchers will inject “phages” (virus-like molecules that each carry a unique protein fragment) into the bloodstreams of the mice. The phages are small enough to pass through the BBB and are created to attach to a specific proteins on the brain blood cells. Dr. Giordano’s team will collect brain tissue samples from the mice and collect the phages to understand what proteins the phages bound to narrow down the number of potential brain blood vessel biomarkers Their goal is to identify promising protein biomarkers that might be used for the development of precision medicine therapies and diagnostic tools.
Impact
This study investigates brain blood vessel biomarkers that might be tested as therapeutic targets for conditions that affect the brain. Results could inform development of new targets for Alzheimer’s treatments.