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

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 br...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072949/
https://www.ncbi.nlm.nih.gov/pubmed/32059400
http://dx.doi.org/10.3390/ijms21041225
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author 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.
author_facet 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.
author_sort Owasil, Raisah
collection PubMed
description 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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spelling pubmed-70729492020-03-19 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. Int J Mol Sci Article 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. MDPI 2020-02-12 /pmc/articles/PMC7072949/ /pubmed/32059400 http://dx.doi.org/10.3390/ijms21041225 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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.
The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy
title The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy
title_full The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy
title_fullStr The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy
title_full_unstemmed The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy
title_short The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy
title_sort pattern of aqp4 expression in the ageing human brain and in cerebral amyloid angiopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072949/
https://www.ncbi.nlm.nih.gov/pubmed/32059400
http://dx.doi.org/10.3390/ijms21041225
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