Data files

Age-related decline in brain endothelial cell (BEC) function critically contributes to cerebrovascular and neurodegenerative 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 (MACS)-based mouse BEC enrichment protocol compatible with high-resolution mass-spectrometry and analysed the profiles of protein abundance ...

The Beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. To discover potential BAC2 substrates in plasma, mice were treated with a non-specific BACE inhibitor (Cpd89) and a BACE1 preferring inhibitor (LY2811376). Plasma proteomics using DIA showed a reduced abundance of soluble FLT4 (sVEGFR3) for the non-specific ...

The beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we performed discovery proteomics to identify substrates of the protease BACE2 in plasma of mice. Therefore, we analysed plasma from BACE2 KO, and WT controls. Inactivation of BACE2 inhibited shedding of VEGFR3/FLT4. Thus, sVEGFR3 represents a ...

The beta-secretase BACE1 is a central drug target for Alzheimer’s disease. Clinically tested, BACE1-directed inhibitors also block the homologous protease BACE2. Yet, little is known about physiological BACE2 substrates and functions in vivo. Here, we performed glycoprotein enrichment and subsequent discovery proteomics to identify substrates of the protease BACE2 in plasma of mice. Therefore, we analysed plasma from BACE2 KO, BACE1/2 double KO and WT controls, as well as BACE1 KO with a separate ...