M Leite, Diana;
Seifi, Mohsen;
Ruiz-Perez, Lorena;
Nguemo, Filomain;
Plomann, Markus;
Swinny, Jerome D;
Battaglia, Giuseppe;
(2022)
Syndapin-2 mediated transcytosis of amyloid-β across the blood-brain barrier.
Brain Communications
, 4
(1)
, Article fcac039. 10.1093/braincomms/fcac039.
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Abstract
A deficient transport of amyloid-β across the blood-brain barrier, and its diminished clearance from the brain, contribute to neurodegenerative and vascular pathologies, such as Alzheimer's disease and cerebral amyloid angiopathy, respectively. At the blood-brain barrier, amyloid-β efflux transport is associated with the low-density lipoprotein receptor-related protein 1. However, the precise mechanisms governing amyloid-β transport across the blood-brain barrier, in health and disease, remain to be fully understood. Recent evidence indicates that the low-density lipoprotein receptor-related protein 1 transcytosis occurs through a tubulation-mediated mechanism stabilized by syndapin-2. Here, we show that syndapin-2 is associated with amyloid-β clearance via low-density lipoprotein receptor-related protein 1 across the blood-brain barrier. We further demonstrate that risk factors for Alzheimer's disease, amyloid-β expression and ageing, are associated with a decline in the native expression of syndapin-2 within the brain endothelium. Our data reveals that syndapin-2-mediated pathway, and its balance with the endosomal sorting, are important for amyloid-β clearance proposing a measure to evaluate Alzheimer's disease and ageing, as well as a target for counteracting amyloid-β build-up. Moreover, we provide evidence for the impact of the avidity of amyloid-β assemblies in their trafficking across the brain endothelium and in low-density lipoprotein receptor-related protein 1 expression levels, which may affect the overall clearance of amyloid-β across the blood-brain barrier.
Type: | Article |
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Title: | Syndapin-2 mediated transcytosis of amyloid-β across the blood-brain barrier |
Location: | England |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1093/braincomms/fcac039 |
Publisher version: | https://doi.org/10.1093/braincomms/fcac039 |
Language: | English |
Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
Keywords: | Alzheimer’s disease, Syndapin-2, amyloid-β, blood–brain barrier, tubular transcytosis |
UCL classification: | UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry UCL > Provost and Vice Provost Offices > UCL BEAMS UCL |
URI: | https://discovery.ucl.ac.uk/id/eprint/10147001 |
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