The choroid plexus is a source of active renin in the central nervous system

The renin-angiotensin system is important in cardiovascular and brain physiology. The local brain RAS was proposed over 50 years and decades of research support its existence. However, it remains controversial primarily due to disputed identification of functional renin in the central nervous system. Here, we show that functional renin is produced and released by the choroid plexus, the primary source of cerebrospinal fluid in the brain. Across public RNA sequencing datasets, renin is expressed in both mouse and human choroid plexus epithelial cells, and its expression is validated by RNAscope, immunofluorescence, qPCR, and western blotting. We further demonstrate renin activity in human cerebrospinal fluid that is independent of either circulating renin or blood-brain barrier integrity and confirm its release and activity from mouse choroid plexus explants. Notably, cerebrospinal fluid renin activity but not plasma renin activity increases with aging in human adults. These findings identify the choroid plexus as a source of renin in the central nervous system and provide evidence supporting a local functional brain renin angiotensin system.