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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7072949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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