The brain has a cleanup system that moves waste out along tiny channels around blood vessels and through lymph-like vessels in the tough covering of the brain (the “dura”). In Alzheimer’s disease (AD), harmful proteins build up in the brain. Many scientists think that slower or blocked clearance, along with extra production, helps drive this build-up. Our project will show what healthy clearance looks like and how it changes with normal aging. In volunteers, we will follow a standard MRI dye after it is given in two ways: into the spinal fluid and into a vein. Both procedures will be performed under carefully monitored, approved protocols. Repeated brain scans at very high resolution will let us watch where the dye travels: between brain tissue, the fluid around the brain, the dura, and the “bridging veins” that drain toward the skull. We will also measure thousands of proteins in blood and spinal fluid to see whether certain protein patterns reflect how well the brain clears waste on the scans. From these data, we will create the first detailed reference values for healthy adults across a wide age range. These reference values, together with simple imaging measures, are designed to spot early warning signs of clearance problems long before memory symptoms appear. The results will guide future studies in people at risk for AD and help test treatments that aim to reopen the brain’s natural drainage pathways.
