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Open AccessArticle

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

1
Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
2
Sheffield Institute for Translational Neurosciences, University of Sheffield, Sheffield S10 2HQ, UK
3
Academic Neuropathology, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
4
Translational and Clinical Research, Newcastle University, Newcastle NE2 4HH, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(4), 1225; https://doi.org/10.3390/ijms21041225
Received: 24 December 2019 / Revised: 3 February 2020 / Accepted: 10 February 2020 / Published: 12 February 2020
(This article belongs to the Special Issue Cerebral Amyloid Angiopathy: Causes, Diagnosis and Treatment)
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.
Keywords: aquaporin 4; cerebral amyloid angiopathy; white matter hyperintensities; grey matter; white matter aquaporin 4; cerebral amyloid angiopathy; white matter hyperintensities; grey matter; white matter
MDPI and ACS Style

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. The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy. Int. J. Mol. Sci. 2020, 21, 1225.

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