Interaction between blood-brain barrier and glymphatic system in solute clearance

I. C. M. Verheggen*, M. P. J. Van Boxtel, F. R. J. Verhey, J. F. A. Jansen, W. H. Backes

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

58 Citations (Web of Science)

Abstract

Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-beta, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-beta accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalNeuroscience and Biobehavioral Reviews
Volume90
DOIs
Publication statusPublished - Jul 2018

Keywords

  • Blood-brain barrier
  • BBB
  • Glymphatic system
  • Clearance
  • Amyloid-beta
  • Alzheimer's disease
  • Imaging
  • SMALL VESSEL DISEASE
  • AMYLOID CASCADE HYPOTHESIS
  • CENTRAL-NERVOUS-SYSTEM
  • ALZHEIMERS-DISEASE
  • CEREBROSPINAL-FLUID
  • MOUSE MODEL
  • BETA-PEPTIDE
  • A-BETA
  • TRANSPORT
  • DEMENTIA

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