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Vascular α1a adrenergic receptors as a potential therapeutic target for ipad in alzheimer’s disease

Lookup NU author(s): Professor Johannes Attems



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2020 by the authors. Licensee MDPI, Basel, Switzerland.Drainage of interstitial fluid from the brain occurs via the intramural periarterial drainage (IPAD) pathways along the basement membranes of cerebral capillaries and arteries against the direction of blood flow into the brain. The cerebrovascular smooth muscle cells (SMCs) provide the motive force for driving IPAD, and their decrease in function may explain the deposition of amyloid-beta as cerebral amyloid angiopathy (CAA), a key feature of Alzheimer’s disease. The α-adrenoceptor subtype α1A is abundant in the brain, but its distribution in the cerebral vessels is unclear. We analysed cultured human cerebrovascular SMCs and young, old and CAA human brains for (a) the presence of α1A receptor and (b) the distribution of the α1A receptor within the cerebral vessels. The α1A receptor was present on the wall of cerebrovascular SMCs. No significant changes were observed in the vascular expression of the α1A-adrenergic receptor in young, old and CAA cases. The pattern of vascular staining appeared less punctate and more diffuse with ageing and CAA. Our results show that the α1A-adrenergic receptor is preserved in cerebral vessels with ageing and in CAA and is expressed on cerebrovascular smooth muscle cells, suggesting that vascular adrenergic receptors may hold potential for therapeutic targeting of IPAD.

Publication metadata

Author(s): Frost M, Keable A, Baseley D, Sealy A, Zbarcea DA, Gatherer M, Yuen HM, Sharp MM, Weller RO, Attems J, Smith C, Chiarot PR, Carare RO

Publication type: Article

Publication status: Published

Journal: Pharmaceuticals

Year: 2020

Volume: 13

Issue: 9

Pages: 1-14

Online publication date: 22/09/2020

Acceptance date: 19/09/2020

Date deposited: 16/11/2020

ISSN (electronic): 1424-8247

Publisher: MDPI AG


DOI: 10.3390/ph13090261


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Funder referenceFunder name
Alzheimer’s Society
e UK Medical Research Council (G0400074)