PUBLICATION
Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
- Authors
- Jeong, Y.M., Lee, J.G., Cho, H.J., Lee, W.S., Jeong, J., Lee, J.S.
- ID
- ZDB-PUB-211116-15
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(21): (Journal)
- Registered Authors
- Cho, Hyun-Ju, Lee, Jae-Geun
- Keywords
- Alzheimer’s disease, amyloid beta, brain lymphatic endothelial cells, zebrafish model
- MeSH Terms
-
- Amyloid beta-Peptides/metabolism*
- Animals
- Biological Transport
- Brain/metabolism*
- Cells, Cultured
- Endothelial Cells/metabolism*
- Zebrafish/metabolism*
- PubMed
- 34769316 Full text @ Int. J. Mol. Sci.
Citation
Jeong, Y.M., Lee, J.G., Cho, H.J., Lee, W.S., Jeong, J., Lee, J.S. (2021) Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish. International Journal of Molecular Sciences. 22(21):.
Abstract
The failure of amyloid beta (Aβ) clearance is a major cause of Alzheimer's disease, and the brain lymphatic systems play a crucial role in clearing toxic proteins. Recently, brain lymphatic endothelial cells (BLECs), a non-lumenized lymphatic cell in the vertebrate brain, was identified, but Aβ clearance via this novel cell is not fully understood. We established an in vivo zebrafish model using fluorescently labeled Aβ42 to investigate the role of BLECs in Aβ clearance. We discovered the efficient clearance of monomeric Aβ42 (mAβ42) compared to oligomeric Aβ42 (oAβ42), which was illustrated by the selective uptake of mAβ42 by BLECs and peripheral transport. The genetic depletion, pharmacological inhibition via the blocking of the mannose receptor, or the laser ablation of BLECs resulted in the defective clearance of mAβ42. The treatment with an Aβ disaggregating agent facilitated the internalization of oAβ42 into BLECs and improved the peripheral transport. Our findings reveal a new role of BLECs in the differential clearance of mAβ42 from the brain and provide a novel therapeutic strategy based on promoting Aβ clearance.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping