A Hidden Epithelial Barrier in the Brain with a Central Role in Regulating Brain Homeostasis Implications for Aging

Despite increasing interest the last years, the choroid plexus still is a relatively understudied tissue in neuroscience. The choroid plexus contains fenestrated capillaries surrounded by tightly connected choroid plexus epithelial cells that form the blood-cerebrospinal fluid barrier. The choroid plexus is the main source of cerebrospinal fluid production, assures removal of toxic waste products, and acts as gatekeeper of the brain by the presence of resident inflammatory cells. Increasing evidence shows that choroid plexus' dysfunction, via altered secretory, transport, immune, and barrier function, plays a central role in a very diverse set of clinical conditions such as aging and the age-associated Alzheimer's disease. Indeed, age-related changes may weaken the barrier formed by the choroid plexus epithelial cells and/or impair the choroid plexus' ability to generate cerebrospinal fluid and to produce beneficial factors. Consequently, advanced knowledge of the choroid plexus-cerebrospinal fluid system in aging is essential to better understand age-associated neurological diseases and might open up new therapeutic strategies.