Berg Brain Entry and Exit Consortium: Patch-Seq Analysis of the Choroid Plexus Epithelial Cell Barrier in Homeostasis and in Alzheimer’s Disease

Blood-brain barriers act as strict control points for what can and cannot enter the brain. Three main barriers exist to protect the brain from the free exchange of substances that are traveling in the bloodstream, making the brain unique compared with other organs of the body. Three main barriers protect the brain: the blood-brain barrier, the blood-cerebrospinal fluid barrier, and the blood-meningeal barrier. The cerebrospinal fluid is the clear, colorless fluid that surrounds the brain and spinal cord. The main function is to supply nutrients to the central nervous system, to protect against trauma and remove waste products. All of these barriers allow the brain to exist in a stable equilibrium. This project intends to study the blood-CSF barrier, which is located in the brain’s ventricles—a network of cavities filled with cerebrospinal fluid. Key cells involved in this system include the choroid plexus epithelial cells, which are cells that produce CSF. Importantly, the blood-CSF barrier is a clearance route that rids the brain of unwanted waste products. Dysfunction in brain barriers has been observed during aging and in neurological conditions such as Alzheimer’s disease. The aim of this proposal is to gain a better understanding of how CSF production impacts the barrier and clearance systems of the brain by studying the blood-CSF barrier at the single-cell level. This study will help understand how choroid plexus cells change during aging and Alzheimer’s disease, and how these changes impact the delivery of producing and delivering CSF to the brain.