Fig. 9.

Schematic diagram of aggravated PD-like pathological progression in A53T mice following blocking brain lymphatic drainage. a In intact condition, AQP4-dependent astroglial water transport facilitates convective bulk flow along para-arterial space-interstitial space-par-venous space routes, which drives clearance of interstitial solutes from the brain parenchyma to enter the subarachnoid CSF, and subsequently transport into meningeal lymphatic vessel-cervical lymph node pathway. b Astrocyte activation caused by excessive production of α-syn impairs AQP4 polarity surrounding microvessels, which reduces glymphatic clearance and subsequently leads to gradual aggregation of α-syn with age in A53T mice. LDclns disrupts meningeal lymphatic clearance of α-syn, further aggravating the above vicious circle and causing dopaminergic neuronal degeneration and motor malfunction