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 to...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00018/full |
| _version_ | 1811255597652246528 |
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| author | Alexandra Katharina Diem Alexandra Katharina Diem Mingyi eTan Neil W. Bressloff Cheryl eHawkes Alan W. J. Morris Alan W. J. Morris Roy O. Weller Roxana O. Carare Roxana O. Carare |
| author_facet | Alexandra Katharina Diem Alexandra Katharina Diem Mingyi eTan Neil W. Bressloff Cheryl eHawkes Alan W. J. Morris Alan W. J. Morris Roy O. Weller Roxana O. Carare Roxana O. Carare |
| author_sort | Alexandra Katharina Diem |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T17:26:15Z |
| format | Article |
| id | doaj.art-63c5a57464cf4220b9f54330765ae548 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-12T17:26:15Z |
| publishDate | 2016-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-63c5a57464cf4220b9f54330765ae5482022-12-22T03:23:17ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652016-02-01810.3389/fnagi.2016.00018174328A Simulation Model of Periarterial Clearance of Amyloid-beta from the BrainAlexandra Katharina Diem0Alexandra Katharina Diem1Mingyi eTan2Neil W. Bressloff3Cheryl eHawkes4Alan W. J. Morris5Alan W. J. Morris6Roy O. Weller7Roxana O. Carare8Roxana O. Carare9University of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonUniversity of SouthamptonThe 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.http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00018/fullBrainCerebral Amyloid AngiopathyDiffusionAlzheimer's diseaseDextransimulation model |
| spellingShingle | Alexandra Katharina Diem Alexandra Katharina Diem Mingyi eTan Neil W. Bressloff Cheryl eHawkes Alan W. J. Morris Alan W. J. Morris Roy O. Weller Roxana O. Carare Roxana O. Carare A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain Frontiers in Aging Neuroscience Brain Cerebral Amyloid Angiopathy Diffusion Alzheimer's disease Dextran simulation model |
| title | A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain |
| title_full | A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain |
| title_fullStr | A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain |
| title_full_unstemmed | A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain |
| title_short | A Simulation Model of Periarterial Clearance of Amyloid-beta from the Brain |
| title_sort | simulation model of periarterial clearance of amyloid beta from the brain |
| topic | Brain Cerebral Amyloid Angiopathy Diffusion Alzheimer's disease Dextran simulation model |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00018/full |
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