Data for paper "A simulation model of periarterial clearance of amyloid-beta from the brain"
Data for paper "A simulation model of periarterial clearance of amyloid-beta from the brain"
The accumulation of soluble and insoluble amyloid-beta (A-beta) in the brain indicates failure of elimination of A-beta from the brain with age and Alzheimer's disease. There is a variety of mechanisms for elimination of A-beta from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of A-beta into the blood and periarterial lymphatic drainage of A-beta. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as A-beta, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of A-beta in the walls of human arteries with age and Alzheimer's disease as cerebral amyloid angiopathy (CAA). Initially, A-beta diffuses through the extracellular spaces of grey matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterised, the exact mechanism whereby perivascular elimination of A-beta occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy.
Alzheimer's disease, brain, cerebral amyloid angiopathy, dextran, diffusion, lymphatic drainage, perivascular drainage, simulation model
University of Southampton
Diem, Alexandra, Katharina
4728b96b-482f-4329-ad66-f37edc8fd935
Tan, Mingyi
4d02e6ad-7915-491c-99cc-a1c85348267c
Bressloff, Neil
4f531e64-dbb3-41e3-a5d3-e6a5a7a77c92
HAWKES, CHERYL
031a17ac-0931-4ff9-93cc-df8cb58e14f7
Morris, Alan
e70d7160-c9d9-4035-90b8-9006a1052551
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Diem, Alexandra, Katharina
4728b96b-482f-4329-ad66-f37edc8fd935
Tan, Mingyi
4d02e6ad-7915-491c-99cc-a1c85348267c
Bressloff, Neil
4f531e64-dbb3-41e3-a5d3-e6a5a7a77c92
HAWKES, CHERYL
031a17ac-0931-4ff9-93cc-df8cb58e14f7
Morris, Alan
e70d7160-c9d9-4035-90b8-9006a1052551
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Diem, Alexandra, Katharina, Tan, Mingyi, Bressloff, Neil, HAWKES, CHERYL, Morris, Alan, Weller, Roy O. and Carare, Roxana-Octavia
(2016)
Data for paper "A simulation model of periarterial clearance of amyloid-beta from the brain".
University of Southampton
doi:10.5258/SOTON/386692
[Dataset]
Abstract
The accumulation of soluble and insoluble amyloid-beta (A-beta) in the brain indicates failure of elimination of A-beta from the brain with age and Alzheimer's disease. There is a variety of mechanisms for elimination of A-beta from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of A-beta into the blood and periarterial lymphatic drainage of A-beta. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as A-beta, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of A-beta in the walls of human arteries with age and Alzheimer's disease as cerebral amyloid angiopathy (CAA). Initially, A-beta diffuses through the extracellular spaces of grey matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterised, the exact mechanism whereby perivascular elimination of A-beta occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy.
Archive
akdiem_diffusion_data_02db92969346.zip
- Dataset
More information
Published date: 2016
Keywords:
Alzheimer's disease, brain, cerebral amyloid angiopathy, dextran, diffusion, lymphatic drainage, perivascular drainage, simulation model
Organisations:
Electronics & Computer Science, Fluid Structure Interactions Group, Computational Engineering & Design Group, Clinical & Experimental Sciences
Projects:
Doctoral Training Centre in Complex Systems Simulations
Funded by: UNSPECIFIED (EP/G03690X/1)
1 October 2009 to 31 March 2018
Identifiers
Local EPrints ID: 386692
URI: http://eprints.soton.ac.uk/id/eprint/386692
PURE UUID: 5d6f6fb0-5ca8-440a-afaf-f70974031ed0
Catalogue record
Date deposited: 02 Feb 2016 11:57
Last modified: 05 Nov 2023 02:36
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Contributors
Creator:
Alexandra, Katharina Diem
Creator:
CHERYL HAWKES
Creator:
Alan Morris
Creator:
Roy O. Weller
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