Blood–Brain Barrier Dysfunction in a 3D In Vitro Model of Alzheimer's Disease
Name
advs.201900962.pdf
Description
Published version
Size
2.37 MB
Format
Adobe PDF
Checksum (MD5)
926bd62bcde8d5c2655122ee3789c176
Author(s)
Shin, Yoojin
Choi, Se Hoon
Kim, Eunhee
Bylykbashi, Enjana
Kim, Jeong Ah
Chung, Seok
Kim, Doo Yeon
Kamm, Roger Dale
Tanzi, Rudolph E.
Date Issued
August 2019
Journal
Advanced Science
Publisher
Wiley
Citation
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
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Singapore-MIT Alliance in Research and Technology (SMART)
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/advs.201900962
