Team: Ronald van Kesteren, Betty Tijms, Michiel Pegtel, Wiep Scheper, Connie Jimenez

Brain disorders are difficult to diagnose or treat with precision. Due to the delicate nature of the brain and its relative inaccessibility to surgical procedures, clinicians rely mostly on noninvasive brain imaging technologies to establish a diagnosis or monitor treatment outcome. Detailed molecular characterization of pathological alterations at the cellular level would greatly benefit diagnosis and potentially result in better treatments that can be tailored towards individual patients. The aim of this project is to further improve the use and the interpretation of cerebrospinal fluid (CSF) biomarkers as predictors of disease pathogenesis and to use that information to develop precision medicine for heterogeneous brain disorders. Specifically, we will focus on one particular CSF constituent, namely extracellular vesicles (EVs). EVs are released from brain cells and their content reflects not only their cellular origin but also the biological disease) state of the cells in question. We will perform proteomic profiling of EVs derived from CSF of Alzheimer’s disease (AD) patients and of patients with glioma tumors. In parallel, we will extract and analyze EVs released by brain cells and tumor tissues derived from the very same patients, allowing for the first time to link CSF proteomic profiles to cell type- and tissue-specific pathophysiological mechanisms. Our project will thus significantly contribute to better, biologically informed, biomarkers for AD and glioma as well as new insights into the underlying disease mechanisms. Our findings will be relevant for many other brain diseases as well.