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Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer’s Disease

1
Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
2
Translational and Clinical Research Institute, Newcastle University, Newacstle upon Tyne NE4 5PL, UK
3
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
4
Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY 13902, USA
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2020, 13(9), 261; https://doi.org/10.3390/ph13090261
Received: 17 August 2020 / Revised: 14 September 2020 / Accepted: 19 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue New Drugs and Biologics For Treatment of Central Nervous Dysfunction)
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. View Full-Text
Keywords: α1A adrenergic receptor; intramural periarterial drainage; cerebral blood vessels α1A adrenergic receptor; intramural periarterial drainage; cerebral blood vessels
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MDPI and ACS Style

Frost, M.; Keable, A.; Baseley, D.; Sealy, A.; Andreea Zbarcea, D.; Gatherer, M.; Yuen, H.M.; Sharp, M.M.; Weller, R.O.; Attems, J.; Smith, C.; Chiarot, P.R.; Carare, R.O. Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer’s Disease. Pharmaceuticals 2020, 13, 261. https://doi.org/10.3390/ph13090261

AMA Style

Frost M, Keable A, Baseley D, Sealy A, Andreea Zbarcea D, Gatherer M, Yuen HM, Sharp MM, Weller RO, Attems J, Smith C, Chiarot PR, Carare RO. Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer’s Disease. Pharmaceuticals. 2020; 13(9):261. https://doi.org/10.3390/ph13090261

Chicago/Turabian Style

Frost, Miles, Abby Keable, Dan Baseley, Amber Sealy, Diana Andreea Zbarcea, Maureen Gatherer, Ho M. Yuen, Matt M. Sharp, Roy O. Weller, Johannes Attems, Colin Smith, Paul R. Chiarot, and Roxana O. Carare 2020. "Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer’s Disease" Pharmaceuticals 13, no. 9: 261. https://doi.org/10.3390/ph13090261

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