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The pattern of AQP4 expression in the ageing human brain and in cerebral amyloid angiopathy

The pattern of AQP4 expression in the ageing human brain and in cerebral amyloid angiopathy
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 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.

Aquaporin 4, Cerebral amyloid angiopathy, Grey matter, White matter, White matter hyperintensities
1422-0067
Owasil, Raisah
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O'Neill, Ronan
639dce71-1b32-473f-ba04-17d8c4d42067
Keable, Abby
175d97e8-3baf-4130-94a8-f981810e2c96
Nimmo, Jacqui
222608e3-256e-4ba4-a259-cbdfcb5340c6
MacGregor Sharp, Matthew
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Kelly, Louise
a73e3582-a03e-492f-b164-bf1de4b7600d
Saito, Satoshi
fbdde2f6-451c-4b8a-8f48-eb3e55006b7c
Simpson, Julie E
4f5435d8-fc27-40f2-be80-2bf40569cd7d
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Smith, Colin
d991039c-1c8b-4aff-a306-b45c67c486e9
Attems, Johannes
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Wharton, Stephen B
dc1ee8f7-ec50-4cb2-983c-4156a50a2005
Yuen, Ho Ming
b1df4c57-0c2a-44ac-ab40-22b88e8effe8
Carare, Roxana O
0478c197-b0c1-4206-acae-54e88c8f21fa
Owasil, Raisah
34eccf6e-be47-49c0-adee-55d9fbb19e8f
O'Neill, Ronan
639dce71-1b32-473f-ba04-17d8c4d42067
Keable, Abby
175d97e8-3baf-4130-94a8-f981810e2c96
Nimmo, Jacqui
222608e3-256e-4ba4-a259-cbdfcb5340c6
MacGregor Sharp, Matthew
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Kelly, Louise
a73e3582-a03e-492f-b164-bf1de4b7600d
Saito, Satoshi
fbdde2f6-451c-4b8a-8f48-eb3e55006b7c
Simpson, Julie E
4f5435d8-fc27-40f2-be80-2bf40569cd7d
Weller, Roy O
4a501831-e38a-4d39-a125-d7141d6c667b
Smith, Colin
d991039c-1c8b-4aff-a306-b45c67c486e9
Attems, Johannes
03a5a37f-79eb-4350-b6ab-ffa1999279ab
Wharton, Stephen B
dc1ee8f7-ec50-4cb2-983c-4156a50a2005
Yuen, Ho Ming
b1df4c57-0c2a-44ac-ab40-22b88e8effe8
Carare, Roxana O
0478c197-b0c1-4206-acae-54e88c8f21fa

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 and Carare, Roxana O (2020) The pattern of AQP4 expression in the ageing human brain and in cerebral amyloid angiopathy. International Journal of Molecular Sciences, 21 (4), [1225]. (doi:10.3390/ijms21041225).

Record type: Article

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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More information

Accepted/In Press date: 10 February 2020
Published date: 12 February 2020
Keywords: Aquaporin 4, Cerebral amyloid angiopathy, Grey matter, White matter, White matter hyperintensities

Identifiers

Local EPrints ID: 442819
URI: http://eprints.soton.ac.uk/id/eprint/442819
ISSN: 1422-0067
PURE UUID: 5dc6f403-72eb-4dbe-9b08-b541dd1ccb25
ORCID for Matthew MacGregor Sharp: ORCID iD orcid.org/0000-0002-6623-5078
ORCID for Roxana O Carare: ORCID iD orcid.org/0000-0001-6458-3776

Catalogue record

Date deposited: 28 Jul 2020 16:31
Last modified: 26 Nov 2021 02:55

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Contributors

Author: Raisah Owasil
Author: Ronan O'Neill
Author: Abby Keable
Author: Jacqui Nimmo
Author: Matthew MacGregor Sharp ORCID iD
Author: Louise Kelly
Author: Satoshi Saito
Author: Julie E Simpson
Author: Roy O Weller
Author: Colin Smith
Author: Johannes Attems
Author: Stephen B Wharton
Author: Ho Ming Yuen
Author: Roxana O Carare ORCID iD

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