z-logo
Premium
Loss of perivascular aquaporin‐4 in idiopathic normal pressure hydrocephalus
Author(s) -
HasanOlive Md Mahdi,
Enger Rune,
Hansson HansArne,
Nagelhus Erlend A.,
Eide Per Kristian
Publication year - 2019
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23528
Subject(s) - glymphatic system , aquaporin 4 , parenchyma , pathology , perivascular space , neurodegeneration , cerebrospinal fluid , medicine , hydrocephalus , neuroscience , biology , disease , radiology
Abstract 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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here