Glymphatic System Impairment in Alzheimer’s Disease and Idiopathic Normal Pressure Hydrocephalus

Abstract

~10% of dementia patients have idiopathic normal pressure hydrocephalus (iNPH), an expansion of the cerebrospinal fluid (CSF)-filled brain ventricles. iNPH and Alzheimer’s disease (AD) both exhibit sleep disturbances, build-up of brain metabolic wastes and Aβ plaques, perivascular reactive astrogliosis, and mislocalization of astrocyte Aquaporin-4 (AQP4). The glymphatic system facilitates brain fluid clearance and waste removal during sleep via glia-supported perivascular channels. Human studies have implicated impaired glymphatic function in both AD and iNPH. Continued investigation into the role of glymphatic system biology in AD and iNPH models could lead to new strategies to improve brain health by restoring homeostatic brain metabolism and CSF dynamics.