Fig. 1

Schematic of CSF circulation, CSF outflow systems, and the anatomy of various CSF compartments. CSF is produced by the choroid plexus in the ventricles, where it delivers growth factors to progenitor cells that originate on the surface of the ventricles, and then proliferate into neurons and migrate to form the cerebral cortex. CSF circulates from the lateral, third and fourth ventricles to the cisterns of the brain, and then flows into the subarachnoid space, where it envelops the cortical convexities of the brain (EA-CSF). Inset box: From the subarachnoid space, there is retrograde influx of CSF into the parenchyma, where CSF and interstitial fluid interact in the perivascular space, alongside blood vessels that course throughout the brain. Astrocytes lining the perivascular space aid in transporting fluid that removes inflammatory waste proteins (e.g., Aβ), which are continually secreted by neurons as byproducts of neuronal activity and would otherwise build up in the brain. Finally, fluid carrying these inflammatory waste products returns to the subarachnoid space (EA-CSF) and drains into meningeal lymphatic vessels and arachnoid granulations.