In both Alzheimer’s disease (AD) and glioma, many molecular processes are disrupted, but the precise underlying mechanisms remain largely unknown. Recent advances in proteomic techniques have made it possible to study molecular complexity of these disorders in more detail and have revealed that distinct disease subtypes may exist in these disorders that each require subtype-specific therapy.
The aim of this project is to further understand the underlying mechanisms of subtype-specific molecular alterations in CSF by investigating protein and RNA alterations in 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. 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 molecular profiles to cell type- and tissue-specific pathophysiological mechanisms.
You will develop, in a team with world experts, novel techniques for EV extraction from CSF of AD patients and of patients with glioma tumors, and perform proteomic and transcriptomic profiling of EVs. With this data you will be able to further our knowledge of the common and unique aspects of these brain disorders to better understand specific pathogenic mechanisms. The project will thus significantly contribute to new insights into the underlying disease mechanisms in AD and glioma, which may translate directly into biomarkers that could have use in the clinic.