Peri-arterial pathways for clearance of α-Synuclein and tau from the brain: implications for the pathogenesis of dementias and for immunotherapy
Peri-arterial pathways for clearance of α-Synuclein and tau from the brain: implications for the pathogenesis of dementias and for immunotherapy
Introduction: Accumulation of amyloid beta (Aβ), α-synuclein (αSyn), and tau in dementias indicates their age-related failure of elimination from the brain. Aβ is eliminated along basement membranes in walls of cerebral arterioles and leptomeningeal arteries (intramural peri-arterial drainage [IPAD]); IPAD is impaired with age. We test the hypothesis that αSyn and tau are also eliminated from the normal brain along IPAD pathways.
Methods: Soluble αSyn or tau was injected into mouse hippocampus. Animals were perfused 5 minutes to 7 days post-injection. Blood vessels were identified by ROX-SE for light-sheet and immunolabeling for confocal microscopy. IPAD was quantified by measuring the proportion of arterioles with αSyn/tau.
Results: αSyn and tau are eliminated from the brain by IPAD but with different dynamics.
Discussion: Age-related failure of IPAD may play a role in the pathogenesis of synucleinopathies and tauopathies. αSyn persists within IPAD at 24 hours, which may affect immunotherapy for αSyn.
Nimmo, Jacqui Taryn
222608e3-256e-4ba4-a259-cbdfcb5340c6
Johnston, David
b41163c9-b9d2-425c-af99-2a357204014e
Dodart, J.C.
7e5f6861-a4e2-4ee7-8d2d-576274e92dc6
MacGregor Sharp, Matthew
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Verma, Ajay
5a207350-0de9-487a-be28-f9eb2f558140
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
2020
Nimmo, Jacqui Taryn
222608e3-256e-4ba4-a259-cbdfcb5340c6
Johnston, David
b41163c9-b9d2-425c-af99-2a357204014e
Dodart, J.C.
7e5f6861-a4e2-4ee7-8d2d-576274e92dc6
MacGregor Sharp, Matthew
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Verma, Ajay
5a207350-0de9-487a-be28-f9eb2f558140
Carare, Roxana-Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Nimmo, Jacqui Taryn, Johnston, David, Dodart, J.C., MacGregor Sharp, Matthew, Weller, Roy O., Nicoll, James, Verma, Ajay and Carare, Roxana-Octavia
(2020)
Peri-arterial pathways for clearance of α-Synuclein and tau from the brain: implications for the pathogenesis of dementias and for immunotherapy.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 12 (1), [e12070].
(doi:10.1002/dad2.12070).
Abstract
Introduction: Accumulation of amyloid beta (Aβ), α-synuclein (αSyn), and tau in dementias indicates their age-related failure of elimination from the brain. Aβ is eliminated along basement membranes in walls of cerebral arterioles and leptomeningeal arteries (intramural peri-arterial drainage [IPAD]); IPAD is impaired with age. We test the hypothesis that αSyn and tau are also eliminated from the normal brain along IPAD pathways.
Methods: Soluble αSyn or tau was injected into mouse hippocampus. Animals were perfused 5 minutes to 7 days post-injection. Blood vessels were identified by ROX-SE for light-sheet and immunolabeling for confocal microscopy. IPAD was quantified by measuring the proportion of arterioles with αSyn/tau.
Results: αSyn and tau are eliminated from the brain by IPAD but with different dynamics.
Discussion: Age-related failure of IPAD may play a role in the pathogenesis of synucleinopathies and tauopathies. αSyn persists within IPAD at 24 hours, which may affect immunotherapy for αSyn.
Text
DADM-D-20-00101_R1
- Accepted Manuscript
More information
Accepted/In Press date: 22 June 2020
e-pub ahead of print date: 28 July 2020
Published date: 2020
Additional Information:
© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
Identifiers
Local EPrints ID: 442059
URI: http://eprints.soton.ac.uk/id/eprint/442059
ISSN: 2352-8729
PURE UUID: 41570b5d-7fee-48d6-9191-a6a8e2e2cfbc
Catalogue record
Date deposited: 06 Jul 2020 16:31
Last modified: 17 Mar 2024 05:41
Export record
Altmetrics
Contributors
Author:
Jacqui Taryn Nimmo
Author:
David Johnston
Author:
J.C. Dodart
Author:
Matthew MacGregor Sharp
Author:
Roy O. Weller
Author:
Ajay Verma
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