Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease
Harmful materials in the blood are prevented from entering the healthy brain by a highly selective blood–brain barrier (BBB), and impairment of barrier function has been associated with a variety of neurological diseases. In Alzheimer's disease (AD), BBB breakdown has been shown to occur even b...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021
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| Online Access: | https://hdl.handle.net/1721.1/129477 |
| _version_ | 1826197618808586240 |
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| author | Shin, Yoojin Choi, Se Hoon Kim, Eunhee Bylykbashi, Enjana Kim, Jeong Ah Chung, Seok Kim, Doo Yeon Kamm, Roger Dale Tanzi, Rudolph E. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Shin, Yoojin Choi, Se Hoon Kim, Eunhee Bylykbashi, Enjana Kim, Jeong Ah Chung, Seok Kim, Doo Yeon Kamm, Roger Dale Tanzi, Rudolph E. |
| author_sort | Shin, Yoojin |
| collection | MIT |
| description | Harmful materials in the blood are prevented from entering the healthy brain by a highly selective blood–brain barrier (BBB), and impairment of barrier function has been associated with a variety of neurological diseases. In Alzheimer's disease (AD), BBB breakdown has been shown to occur even before cognitive decline and brain pathology. To investigate the role of the cerebral vasculature in AD, a physiologically relevant 3D human neural cell culture microfluidic model is developed having a brain endothelial cell monolayer with a BBB-like phenotype. This model is shown to recapitulate several key aspects of BBB dysfunction observed in AD patients: increased BBB permeability, decreased expression of claudin-1, claudin-5, and VE-cadherin, increased expression of matrix-metalloproteinase-2 and reactive oxygen species, and deposition of β-amyloid (Aβ) peptides at the vascular endothelium. Thus, it provides a well-controlled platform for investigating BBB function as well as for screening of new drugs that need to pass the BBB to gain access to neural tissues. |
| first_indexed | 2024-09-23T10:50:24Z |
| format | Article |
| id | mit-1721.1/129477 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:50:24Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1294772022-09-27T15:23:41Z Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease Shin, Yoojin Choi, Se Hoon Kim, Eunhee Bylykbashi, Enjana Kim, Jeong Ah Chung, Seok Kim, Doo Yeon Kamm, Roger Dale Tanzi, Rudolph E. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Singapore-MIT Alliance in Research and Technology (SMART) Harmful materials in the blood are prevented from entering the healthy brain by a highly selective blood–brain barrier (BBB), and impairment of barrier function has been associated with a variety of neurological diseases. In Alzheimer's disease (AD), BBB breakdown has been shown to occur even before cognitive decline and brain pathology. To investigate the role of the cerebral vasculature in AD, a physiologically relevant 3D human neural cell culture microfluidic model is developed having a brain endothelial cell monolayer with a BBB-like phenotype. This model is shown to recapitulate several key aspects of BBB dysfunction observed in AD patients: increased BBB permeability, decreased expression of claudin-1, claudin-5, and VE-cadherin, increased expression of matrix-metalloproteinase-2 and reactive oxygen species, and deposition of β-amyloid (Aβ) peptides at the vascular endothelium. Thus, it provides a well-controlled platform for investigating BBB function as well as for screening of new drugs that need to pass the BBB to gain access to neural tissues. 2021-01-20T19:09:07Z 2021-01-20T19:09:07Z 2019-08 2019-06 2020-08-17T17:12:08Z Article http://purl.org/eprint/type/JournalArticle 2198-3844 https://hdl.handle.net/1721.1/129477 Shin, Yoojin et al. "Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease." Advanced Science 6, 20 (August 2019): 1900962. © 2019 The Authors en http://dx.doi.org/10.1002/advs.201900962 Advanced Science Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Shin, Yoojin Choi, Se Hoon Kim, Eunhee Bylykbashi, Enjana Kim, Jeong Ah Chung, Seok Kim, Doo Yeon Kamm, Roger Dale Tanzi, Rudolph E. Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease |
| title | Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease |
| title_full | Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease |
| title_fullStr | Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease |
| title_full_unstemmed | Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease |
| title_short | Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease |
| title_sort | blood brain barrier dysfunction in a 3d in vitro model of alzheimer s disease |
| url | https://hdl.handle.net/1721.1/129477 |
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