A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β

Using in vivo two-photon imaging in mice, the authors traced cerebrospinal fluid entering the brain along channels surrounding penetrating arteries, bounded by astrocytic endfeet, and exchanging with interstitial fluid to carry solutes — including amyloid-β — out through perivenous routes. This convective exchange was shown to depend on aquaporin-4 water channels on astrocytes; genetic deletion of AQP4 markedly slowed solute clearance. The paper named this brain-wide waste-clearance network the glymphatic system and positioned it as the brain's missing lymphatic equivalent.