Neuroinflammation Contributions to Alzheimer’s Disease: Role of the Choroid Plexus

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 access to the brain. A contribution of neuroinflammation to AD pathology is well known but difficult to discern, because aspects of this complex process may be helpful or hurtful 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 ongoing analyses in bacterial and viral models of central nervous system inflammation, we will use our real-time in vivo imaging system to study inflammation at the ChP in the AD mouse model. Parallel histological analyses in ChP tissue from mouse and human AD patients will reveal the degree to which cellular changes are conserved. These analyses will reveal a time point for transcriptomic analysis of the mouse AD ChP, which will provide greater understanding of cell-cell interactions that are disrupted at the molecular level during disease progression.