The Brain's Glymphatic System: Current Controversies

Trends Neurosci. 2020 Jul;43(7):458-466. doi: 10.1016/j.tins.2020.04.003. Epub 2020 May 15.


The glymphatic concept along with the discovery of meningeal lymphatic vessels have, in recent years, highlighted that fluid is directionally transported within the central nervous system (CNS). Imaging studies, as well as manipulations of fluid transport, point to a key role of the glymphatic-lymphatic system in clearance of amyloid-β and other proteins. As such, the glymphatic-lymphatic system represents a new target in combating neurodegenerative diseases. Not unexpectedly, introduction of a new plumbing system in the brain has stirred controversies. This opinion article will highlight what we know about the brain's fluid transport systems, where experimental data are lacking, and what is still debated.

Keywords: amyloid-β; aquaporin-4; brain clearance; cerebrospinal fluid; glymphatic system; meningeal lymphatics; perivascular spaces.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Brain
  • Central Nervous System
  • Glymphatic System*
  • Humans
  • Lymphatic Vessels*
  • Neurodegenerative Diseases*