As detailed in our recent study, 14 these findings demonstrate that AQP4-dependent bulk flow couples CSF influx along the para-arterial pathway to ISF clearance along the paravenous route, forming an organ-wide system that facilitates the clearance of interstitial solutes from the brain parenchyma. On the basis of this glial dependence and the functional and structural homology to the peripheral lymphatic system, we have termed this glio-vascular pathway the glymphatic system (Figure 1A).

Soluble amyloid β (Aβ) is present in the ISF of the healthy young brain and the failure of Aβ clearance is thought to underlie the deposition of Aβ plaques associated with Alzheimer disease progression. 10, 11 We next evaluated whether soluble Aβ constitutes one of the solutes cleared from the brain interstitium along the glymphatic pathway. When fluorescently labeled Aβ was injected into the cortex or striatum, it accumulated around the same paravascular pathways observed with other fluorescent tracers. 14 We also measured the clearance of radiolabeled Aβ injected directly into the striatum of wildtype and Aqp4-null mice. In Aqp4-null mice, radiolabeled Aβ clearance was reduced by≈ 65% compared with wild-type mice, suggesting that AQP4-dependent bulk flow along the