Differential clearance of Aβ species from the brain by brain lymphatic endothelial cells in zebrafish

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Title
Differential clearance of Aβ species from the brain by brain lymphatic endothelial cells in zebrafish
Author(s)
Yun-Mi Jeong; Jae-Geun Lee; Hyun-Ju Cho; Wang Sik Lee; Jinyoung JeongJeong Soo Lee
Bibliographic Citation
International Journal of Molecular Sciences, vol. 22, no. 21, pp. 11883-11883
Publication Year
2021
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.
Keyword
Alzheimer’s diseaseAmyloid betaBrain lymphatic endothelial cellsZebrafish model
ISSN
1661-6596
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms222111883
Type
Article
Appears in Collections:
Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
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