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The disruption of the blood–brain barrier (BBB) in Alzheimer’s Disease (AD) is largely influenced by amyloid beta (Aβ). In this study, we developed a high-throughput microfluidic BBB model devoid of a physical membrane, featuring endothelial cells interacting with an extracellular matrix (ECM). This paper focuses on the impact of varying concentrations of Aβ1–42 oligomers on BBB dysfunction by treating them in the luminal. Our findings reveal a pronounced accumulation of Aβ1–42 oligomers at the BBB, resulting in the disruption of tight junctions and subsequent leakage evidenced by a barrier integrity assay. Additionally, cytotoxicity assessments indicate a concentration-dependent increase in cell death in response to Aβ1–42 oligomers (LC50 ~ 1 µM). This study underscores the utility of our membrane-free vascular chip in elucidating the dysfunction induced by Aβ with respect to the BBB.
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TERMIS AM
Alzheimer’s disease (AD) is characterized by distinct tissue changes associated with accumulation of extracellular amyloid-beta (Aβ) peptides, and intracellular deposits of phosphorylated Tau (p-tau). There is a clear need to develop 3D AD model for alternative to animal test since current rodent model does not recapitulate complex human AD physiopathology. Here we report on organoid-grafted neurovascular unit (NUV) using 1) spheroid using APP-mutated neuro-progenitor cell and 2) endothelial-based blood brain barrier (BBB) against extracellular matrix. The construct was validated with AD pathology generation and further treatment with β- or γ-secretase inhibitors shows the decrease of Aβ. This paper demonstrates the potential utility of a membrane-free in vitro cortical spheroid tissue construct with BBB in a high throughput platform to model AD.
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- Award ID(s):
- 2100987
- PAR ID:
- 10430430
- Date Published:
- Journal Name:
- Three-dimensional Alzheimer's disease's spheroid grafted neurovascular unit
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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