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Fig. 3 | Translational Neurodegeneration

Fig. 3

From: Propagation of tau and α-synuclein in the brain: therapeutic potential of the glymphatic system

Fig. 3

The glymphatic system in neurodegenerative disease. a An overall view of the glymphatic system and its main components in health (c): the CSF that flows alongside the arteries (from the subarachnoid CSF spaces) moves across the brain parenchyma via convective exchange (yellow chevrons). The movement is driven by pressure gradients and the convective transport is facilitated by a network of glial projections (green cells) and aquaporin-4 channels expressed on their endfeet (red structures). As the CSF passes through the brain parenchyma, it carries the interstitial solutes present in that space towards the perivenous space, from where it gets cleared out of the brain towards meningeal and cervical lymph vessels. b Failure of the glymphatic system in neurodegenerative disease (e.g. d and e): aquaporin-4 becomes depolarised from astrocytic endfeet, leading to reduced convective exchange of paravascular CSF with interstitial fluid. This leads to reduced parenchymal clearance of proteins such as tau (d depicted in blue in the advanced Braak stage Alzheimer’s scenario) and α-synuclein (e depicted in green in the advanced Braak stage Parkinson’s), facilitating their cell-to-cell propagation throughout the brain

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