Studies

Microglial dysfunction is a key pathological feature of Alzheimer´s disease (AD), but little is known about proteome-wide changes in microglia during the course of AD pathogenesis and their consequences for microglial function. Here, we performed an in-depth proteomic characterization of microglia in two AD mouse models, the overexpression APPPS1 and the knock-in AppNL-G-F (APP-KI) model. Proteome changes were followed from pre-deposition to early, middle and advanced stages of amyloid plaque ...

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 ...

Here, we took advantage of well-defined mouse models for β-amyloidosis (APPPS1) to explore proteome changes in the cerebrospinal fluid which are related to these distinct proteopathic lesions. Non-targeted liquid chromatography-mass spectrometry revealed that the majority of proteins that undergo age- and disease-related changes in either mouse model was linked to microglia, and more specifically to previously described disease state-specific microglia transcriptomic signatures. The finding that ...