The University of Southampton
University of Southampton Institutional Repository

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"
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]

Record type: 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.

Text
readme.txt - Text
Available under License Creative Commons Attribution.
Download (2kB)
Archive
akdiem_diffusion_data_02db92969346.zip - Dataset
Available under License Creative Commons Attribution.
Download (1GB)

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
ORCID for Roxana-Octavia Carare: ORCID iD orcid.org/0000-0001-6458-3776

Catalogue record

Date deposited: 02 Feb 2016 11:57
Last modified: 13 Dec 2021 02:44

Export record

Altmetrics

Contributors

Creator: Alexandra, Katharina Diem
Creator: Mingyi Tan
Creator: Neil Bressloff
Creator: CHERYL HAWKES
Creator: Alan Morris
Creator: Roy O. Weller

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×