Connections Between Amyloid Beta and the Meningeal Lymphatics As a Possible Route for Clearance and Therapeutics

Alzheimer's disease (AD) is a complex neurodegenerative disorder causing progressive cognitive decline, memory loss, and death of neural tissue. Current research suggests a connection between bulk flow of interstitial fluid and cerebrospinal fluid across the blood-brain barrier and the recently confirmed meningeal lymphatic channels of the brain. The main symptom of interest in AD is the spontaneous aggregation of amyloid beta (Aβ) proteins resulting from increased production or lack of clearance from brain tissues. These protein aggregates manifest as plaques in the capillary and artery lumina and the neuronal and dural tissues of the brain, and are known to contribute to cerebral amyloid angiopathy and a host of other neuroinflammatory conditions. The meningeal lymphatics contain a substantial population of immune cells and also serve as a drain into the deep cervical lymph nodes. In this study we discuss the molecular mechanisms by which Aβ could gain access to meningeal lymphatic channels through the blood-brain interface, including ways in which it can be cleared to preclude aggregation and plaque deposition.