GliaOct 12, 2018

Loss of water channels around brain blood vessels in normal pressure hydrocephalus

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 29, 2026

Abstract

A significant reduction in AQP4 water channel density was observed in the astrocytic membranes of iNPH patients compared to reference individuals.

Impaired clearance of cerebrospinal fluid (CSF) tracer in iNPH patients may indicate issues with waste solute removal from the brain.
Altered distribution of AQP4 water channels is explored in iNPH, which could affect CSF circulation and waste clearance.
Electron microscopy showed a significantly reduced density of AQP4 in the membranes adjacent to blood vessels in iNPH patients.
A positive correlation exists between AQP4 density near blood vessels and that near brain tissue, though the reduction was not significant toward brain tissue in iNPH.
The findings suggest that reduced perivascular AQP4 expression may contribute to impaired waste clearance and neurodegeneration in iNPH.

Simplified

Idiopathic normal pressure hydrocephalus (iNPH) is a subtype of dementia that may be successfully treated with cerebrospinal fluid (CSF) diversion. Recently, magnetic resonance imaging (MRI) using a MRI contrast agent as a CSF tracer revealed impaired clearance of the CSF tracer from various brain regions such as the entorhinal cortex of iNPH patients. Hampered clearance of waste solutes, for example, soluble amyloid-β, may underlie neurodegeneration and dementia in iNPH. The goal of the present study was to explore whether iNPH is associated with altered subcellular distribution of aquaporin-4 (AQP4) water channels, which is reported to facilitate CSF circulation and paravascular glymphatic drainage of metabolites from the brain parenchyma. Cortical brain biopsies of 30 iNPH patients and 12 reference individuals were subjected to AQP4 immunogold cytochemistry. Electron microscopy revealed significantly reduced density of AQP4 water channels in astrocytic endfoot membranes along cortical microvessels in patients with iNPH versus reference subjects. There was a significant positive correlation between density of AQP4 toward endothelial cells (perivascular) and toward parenchyma, but the reduced density of AQP4 toward parenchyma was not significant in iNPH. We conclude that perivascular AQP4 expression is attenuated in iNPH, potentially contributing to impaired glymphatic circulation, and waste clearance, and subsequent neurodegeneration. Hence, restoring normal perivascular AQP4 distribution may emerge as a novel treatment strategy for iNPH.

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Loss of water channels around brain blood vessels in normal pressure hydrocephalus

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