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The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy

Owasil, Raisah, O’Neill, Ronan, Keable, Abby, Nimmo, Jacqui, MacGregor Sharp, Matthew, Kelly, Louise, Saito, Satoshi, Simpson, Julie E., Weller, Roy O., Smith, Colin, Attems, Johannes, Wharton, Stephen B., Yuen, Ho Ming, Carare, Roxana O.·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21041225PMC PMC7072949
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Abstract

In the absence of lymphatics, fluid and solutes such as amyloid-β (Aβ) are eliminated from the brain along basement membranes in the walls of cerebral capillaries and arteries—the Intramural Peri-Arterial Drainage (IPAD) pathway. IPAD fails with age and insoluble Aβ is deposited as plaques in the brain and in IPAD pathways as cerebral amyloid angiopathy (CAA); fluid accumulates in the white matter as reflected by hyperintensities (WMH) on MRI. Within the brain, fluid uptake by astrocytes is regulated by aquaporin 4 (AQP4). We test the hypothesis that expression of astrocytic AQP4 increases in grey matter and decreases in white matter with onset of CAA. AQP4 expression was quantitated by immunocytochemistry and confocal microscopy in post-mortem occipital grey and white matter from young and old non-demented human brains, in CAA and in WMH. Results: AQP4 expression tended to increase with normal ageing but AQP4 expression in severe CAA was significantly reduced when compared to moderate CAA (p = 0.018). AQP4 expression tended to decline in the white matter with CAA and WMH, both of which are associated with impaired IPAD. Adjusting the level of AQP4 activity may be a valid therapeutic target for restoring homoeostasis in the brain as IPAD fails with age and CAA.

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  • These changes are consistent with astrocytic hypertrophy and suggest a reactive phenotype associated with disrupted lipid metabolism.

    “These changes are consistent with astrocytic hypertrophy and suggest a reactive phenotype associated with disrupted lipid metabolism (Owasil et al. 2020; Dai et al. 2023).”

    From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Owasil et al. 2020

  • AQP4 is abundant in the endfeet of astrocytes that are in contact with cerebral vasculature and pia; this isoform of aquaporin, an integral transmembrane protein, is involved with water-conduction and our levels of expression are associated with reactive gliosis.

    “AQP4 is abundant in the endfeet of astrocytes that are in contact with cerebral vasculature and pia; this isoform of aquaporin, an integral transmembrane protein, is involved with water‐conduction and our levels of expression are associated with reactive gliosis (Owasil et al. 2020; Dai et al. 2023).”

    From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Owasil et al. 2020

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Metadata

Authors
Owasil, R., O’Neill, R., Keable, A., Nimmo, J., MacGregor Sharp, M., Kelly, L., Saito, S., Simpson, J. E., Weller, R. O., Smith, C., Attems, J., Wharton, S. B., Yuen, H. M., & Carare, R. O.
Affiliations
  • Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
  • Sheffield Institute for Translational Neurosciences, University of Sheffield, Sheffield S10 2HQ, UK
  • Academic Neuropathology, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
  • Translational and Clinical Research, Newcastle University, Newcastle NE2 4HH, UK
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-02-12
Volume
21
Issue
4
Pages
1225
ISSN
1422-0067
DOI
10.3390/ijms21041225
PMC
PMC7072949
Cited by
48
References
10
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
British Neuropathological Society (N/A, 00000)

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