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Arterial pulsations cannot drive intramural periarterial drainage: significance for Aβ drainage

Arterial pulsations cannot drive intramural periarterial drainage: significance for Aβ drainage
Arterial pulsations cannot drive intramural periarterial drainage: significance for Aβ drainage
Alzheimer’s Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and Aβ are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness of arterial walls, this pathway fails in its function and Aβ accumulates in the walls of arteries. In this study we tested the hypothesis that arterial pulsations drive IPAD and that a valve mechanism ensures the net drainage in a direction opposite to that of the blood flow. This hypothesis was tested using a mathematical model of the drainage mechanism. We demonstrate firstly that arterial pulsations are not strong enough to produce drainage velocities comparable to experimental observations. Secondly, we demonstrate that a valve mechanism such as directional permeability of the IPAD pathway is necessary to achieve a net reverse flow. The mathematical simulation results are confirmed by assessing the pattern of IPAD in mice using pulse modulators, showing no significant alteration of IPAD. Our results indicate that forces other than the cardiac pulsations are responsible for efficient IPAD.
Alzheimer’s disease, cerebral blood flow, perivascular drainage, intramural periarterial drainage, cerebral lymphatics
1662-4548
Diem, Alexandra
05354aac-509f-47df-a7fb-e157c6a34c72
Macgregor Sharp, Matthew
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Gatherer, Maureen
b0aae216-21c4-4737-b042-865a65658f06
Bressloff, Neil
4f531e64-dbb3-41e3-a5d3-e6a5a7a77c92
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Richardson, Giles
3fd8e08f-e615-42bb-a1ff-3346c5847b91
Diem, Alexandra
05354aac-509f-47df-a7fb-e157c6a34c72
Macgregor Sharp, Matthew
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Gatherer, Maureen
b0aae216-21c4-4737-b042-865a65658f06
Bressloff, Neil
4f531e64-dbb3-41e3-a5d3-e6a5a7a77c92
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Richardson, Giles
3fd8e08f-e615-42bb-a1ff-3346c5847b91

Diem, Alexandra, Macgregor Sharp, Matthew, Gatherer, Maureen, Bressloff, Neil, Carare, Roxana-Octavia and Richardson, Giles (2017) Arterial pulsations cannot drive intramural periarterial drainage: significance for Aβ drainage. Frontiers in Neuroscience, 11. (doi:10.3389/fnins.2017.00475).

Record type: Article

Abstract

Alzheimer’s Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and Aβ are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness of arterial walls, this pathway fails in its function and Aβ accumulates in the walls of arteries. In this study we tested the hypothesis that arterial pulsations drive IPAD and that a valve mechanism ensures the net drainage in a direction opposite to that of the blood flow. This hypothesis was tested using a mathematical model of the drainage mechanism. We demonstrate firstly that arterial pulsations are not strong enough to produce drainage velocities comparable to experimental observations. Secondly, we demonstrate that a valve mechanism such as directional permeability of the IPAD pathway is necessary to achieve a net reverse flow. The mathematical simulation results are confirmed by assessing the pattern of IPAD in mice using pulse modulators, showing no significant alteration of IPAD. Our results indicate that forces other than the cardiac pulsations are responsible for efficient IPAD.

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Accepted/In Press date: 10 August 2017
e-pub ahead of print date: 24 August 2017
Published date: 24 August 2017
Keywords: Alzheimer’s disease, cerebral blood flow, perivascular drainage, intramural periarterial drainage, cerebral lymphatics

Identifiers

Local EPrints ID: 413513
URI: https://eprints.soton.ac.uk/id/eprint/413513
ISSN: 1662-4548
PURE UUID: 888c3db1-f4af-473f-abce-cfeea0d99b4c
ORCID for Alexandra Diem: ORCID iD orcid.org/0000-0003-1719-1942
ORCID for Matthew Macgregor Sharp: ORCID iD orcid.org/0000-0002-6623-5078

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Date deposited: 25 Aug 2017 16:31
Last modified: 10 Dec 2019 01:39

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