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Updated: May 9, 2026

Reliable Isolation of Central Nervous System Microvessels Across Five Vertebrate Groups
Published on: January 12, 2020
Proteomics of mouse brain endothelium uncovers dysregulation of vesicular transport pathways during aging
Katalin Todorov-Völgyi1, Judit González-Gallego2,3, Stephan A Müller4,5
1Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany. katalin.voelgyi@med.uni-muenchen.de.
Abstract:
Age-related decline in brain endothelial cell (BEC) function contributes critically to neurological disease. Comprehensive atlases of the BEC transcriptome have become available, but results from proteomic profiling are lacking. To gain insights into endothelial pathways affected by aging, we developed a magnetic-activated cell sorting-based mouse BEC enrichment protocol compatible with proteomics and resolved the profiles of protein abundance changes during aging. Unsupervised cluster analysis revealed a segregation of age-related protein dynamics with biological functions, including a downregulation of vesicle-mediated transport. We found a dysregulation of key regulators of endocytosis and receptor recycling (most prominently Arf6), macropinocytosis and lysosomal degradation. In gene deletion and overexpression experiments, Arf6 affected endocytosis pathways in endothelial cells. Our approach uncovered changes not picked up by transcriptomic studies, such as accumulation of vesicle cargo and receptor ligands, including Apoe. Proteomic analysis of BECs from Apoe-deficient mice revealed a signature of accelerated aging. Our findings provide a resource for analysing BEC function during aging.
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