Fig. 3

Nonpharmacological effects on the glymphatic and meningeal lymphatic systems in preclinical studies and associated improvements in the disease pathophysiology and behavioral deficits in animal models of AD. Physical exercise (voluntary wheel running), noninvasive brain stimulation (TMS, tPBM, FUS-MB), traditional Chinese medicine (electroacupuncture and Chinese herbal medicine formula Yi-Zhi-Fang-Dai and Xueshuantong), and nutritional supplementation (PUFAs and NBP) have been shown to modulate many factors associated with the glymphatic and meningeal lymphatic systems under physiological conditions (left panel), including the expression of polarized AQP4, CSF glymphatic influx, ISF solute clearance, and the meningeal lymphatics morphology. In animal models of AD, the increased glymphatic and meningeal lymphatic function induced by such nonpharmacological interventions are associated with improvements in the disease pathophysiology (right panel), including reduced Aβ deposition, reactive gliosis, and neuronal loss that culminate with improved learning and memory