Abstract
AbstractAccumulation of amyloid beta protein (Aβ) in brain vessels damages blood brain barrier (BBB) integrity in cerebral amyloid angiopathy (CAA). Macrophage lineage cells scavenge Aβ and produce disease-modifying mediators. Herein, we report that Aβ40-induced macrophage-derived migrasomes are sticky to blood vessels in skin biopsy samples from CAA patients and brain tissue from CAA mouse models (Tg-SwDI/B and 5xFAD mice). We show that CD5L is packed in migrasomes and docked to blood vessels, and that enrichment of CD5L impairs the resistance to complement activation. Increased migrasome-producing capacity of macrophages and membrane attack complex (MAC) in blood are associated with disease severity in both patients and Tg-SwDI/B mice. Of note, complement inhibitory treatment protects against migrasomes-mediated blood-brain barrier injury in Tg-SwDI/B mice. We thus propose that macrophage-derived migrasomes and the consequent complement activation are potential biomarkers and therapeutic targets in CAA.
Funder
National Natural Science Foundation of China
École Nationale d'Ingénieurs de Saint-Etienne
Guangzhou Science and Technology Program key projects
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
2 articles.
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