Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish

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 clea...

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Autores principales:	Yun-Mi Jeong, Jae-Geun Lee, Hyun-Ju Cho, Wang Sik Lee, Jinyoung Jeong, Jeong-Soo Lee
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer’s disease amyloid beta brain lymphatic endothelial cells zebrafish model Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/b72ec3ce4a3245658e66fdf97ebf4795
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spelling	oai:doaj.org-article:b72ec3ce4a3245658e66fdf97ebf47952021-11-11T17:18:20ZDifferential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish10.3390/ijms2221118831422-00671661-6596https://doaj.org/article/b72ec3ce4a3245658e66fdf97ebf47952021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11883https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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.Yun-Mi JeongJae-Geun LeeHyun-Ju ChoWang Sik LeeJinyoung JeongJeong-Soo LeeMDPI AGarticleAlzheimer’s diseaseamyloid betabrain lymphatic endothelial cellszebrafish modelBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11883, p 11883 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer’s disease amyloid beta brain lymphatic endothelial cells zebrafish model Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Alzheimer’s disease amyloid beta brain lymphatic endothelial cells zebrafish model Biology (General) QH301-705.5 Chemistry QD1-999 Yun-Mi Jeong Jae-Geun Lee Hyun-Ju Cho Wang Sik Lee Jinyoung Jeong Jeong-Soo Lee Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
description	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.
format	article
author	Yun-Mi Jeong Jae-Geun Lee Hyun-Ju Cho Wang Sik Lee Jinyoung Jeong Jeong-Soo Lee
author_facet	Yun-Mi Jeong Jae-Geun Lee Hyun-Ju Cho Wang Sik Lee Jinyoung Jeong Jeong-Soo Lee
author_sort	Yun-Mi Jeong
title	Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
title_short	Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
title_full	Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
title_fullStr	Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
title_full_unstemmed	Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish
title_sort	differential clearance of aβ species from the brain by brain lymphatic endothelial cells in zebrafish
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b72ec3ce4a3245658e66fdf97ebf4795
work_keys_str_mv	AT yunmijeong differentialclearanceofabspeciesfromthebrainbybrainlymphaticendothelialcellsinzebrafish AT jaegeunlee differentialclearanceofabspeciesfromthebrainbybrainlymphaticendothelialcellsinzebrafish AT hyunjucho differentialclearanceofabspeciesfromthebrainbybrainlymphaticendothelialcellsinzebrafish AT wangsiklee differentialclearanceofabspeciesfromthebrainbybrainlymphaticendothelialcellsinzebrafish AT jinyoungjeong differentialclearanceofabspeciesfromthebrainbybrainlymphaticendothelialcellsinzebrafish AT jeongsoolee differentialclearanceofabspeciesfromthebrainbybrainlymphaticendothelialcellsinzebrafish
_version_	1718432140796887040

Differential Clearance of Aβ Species from the Brain by Brain Lymphatic Endothelial Cells in Zebrafish

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