Neuroinflammation at the Choroid Plexus in Alzheimer’s Disease

This project seeks to understand the role of the choroid plexus (ChP) in Alzheimer’s disease (AD), especially as it relates to neuroinflammation. The ChP is a highly vascularized structure located within the cerebrospinal fluid–filled compartments deep inside the brain. It forms the principal barrier between the blood and brain fluid. Substances inside this fluid have free access to the brain. The contribution of neuroinflammation to AD pathology is well known but difficult to discern, because aspects of this complex process may be helpful or harmful depending upon when, where and how they take place. Important current efforts are focused mainly on microglia, brain inflammatory immune cells. However, during brain inflammation, many types of peripheral immune cells, including monocytes, neutrophils and lymphocytes, may migrate from the blood into the brain through the ChP, and a fraction of microglia may have originated from the blood. Tissue samples from both AD patients and animals with AD-like symptoms show signs of ChP inflammation and disrupted barrier integrity, and yet the functional state of the ChP and associated immune activities have not been studied extensively in the context of AD. Informed by studies on human ChP samples from AD patients, we will use our groundbreaking real-time in vivo imaging system to study disease progression in mice and elucidate how the ChP brain barrier is altered in AD.