Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease

Yoojin Shin, Se Hoon Choi, Eunhee Kim, Enjana Bylykbashi, Jeong Ah Kim, Seok Chung, Doo Yeon Kim, Roger D. Kamm, Rudolph E. Tanzi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number1900962
JournalAdvanced Science
DOIs
Publication statusPublished - 2019 Jan 1

Fingerprint

blood-brain barrier
Alzheimer Disease
Brain
Claudin-5
Claudin-1
Preclinical Drug Evaluations
Microfluidics
brain
Matrix Metalloproteinase 2
Vascular Endothelium
Amyloid
Permeability
Reactive Oxygen Species
Endothelial cells
Pathology
Endothelial Cells
Cell Culture Techniques
Cell culture
Peptides
Phenotype

Keywords

  • 3D Alzheimer's disease model
  • Alzheimer's disease
  • blood–brain barrier

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Materials Science(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Shin, Y., Choi, S. H., Kim, E., Bylykbashi, E., Kim, J. A., Chung, S., ... Tanzi, R. E. (2019). Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease. Advanced Science, [1900962]. https://doi.org/10.1002/advs.201900962

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 D.; Tanzi, Rudolph E.

In: Advanced Science, 01.01.2019.

Research output: Contribution to journalArticle

Shin, Yoojin ; Choi, Se Hoon ; Kim, Eunhee ; Bylykbashi, Enjana ; Kim, Jeong Ah ; Chung, Seok ; Kim, Doo Yeon ; Kamm, Roger D. ; Tanzi, Rudolph E. / Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease. In: Advanced Science. 2019.
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