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Syndapin-2 mediated transcytosis of amyloid-β across the blood-brain barrier

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. Green open access

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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
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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