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Lookup NU author(s): Professor Johannes Attems
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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.
Author(s): Owasil R, O'Neill R, Keable A, Nimmo J, MacGregor Sharp M, Kelly L, Saito S, Simpson JE, Weller RO, Smith C, Attems J, Wharton SB, Yuen HM, Carare RO
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Year: 2020
Volume: 21
Issue: 4
Pages: 1225
Online publication date: 12/02/2020
Acceptance date: 10/02/2020
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: MDPI
URL: https://doi.org/10.3390/ijms21041225
DOI: 10.3390/ijms21041225
PubMed id: 32059400
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