Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration

Feb 25, 2022The Journal of experimental medicine

The brain's waste system removes harmful tau protein and may protect against its buildup and nerve cell damage

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Abstract

Deletion of aquaporin-4 (AQP4) elevated tau levels in cerebrospinal fluid (CSF) and worsened neurodegeneration in transgenic mice.

  • Tau, a protein linked to neurodegenerative diseases, is actively released into brain interstitial fluid and CSF.
  • AQP4 plays a critical role in the glymphatic system, which clears extracellular tau from the brain.
  • The absence of AQP4 increased tau levels in CSF and led to greater deposition of phosphorylated tau in the brain.
  • Exacerbated neurodegeneration was observed in the brains of mice lacking AQP4 and expressing a mutant form of tau.
  • Findings suggest that impaired glymphatic clearance of extracellular tau may contribute to tau aggregation and neurodegeneration.

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