Metabolic View of Exosomes in Alzheimer’s Disease: Diagnosis, Application and Role in Pathogenesis

• Applicant: Dr. Elisabeth Rackles
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Experimental Models for the Understanding of Nervous System Diseases ; Cell Biology
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 471840646

Alzheimer's disease is an incurable brain disorder that occurs mainly in elderly people. Recently, studies have suggested that exosomes from the central nervous system (CNS) play an important role in the development and progression, diagnosis and treatment of Alzheimer's disease. Exosomes are small vesicles that are released by cells and are involved in the communication between different cells. Exosomes contain a cargo that varies depending on the biological state of the cell. Therefore, the exosomal cargo is considered as a potential source of reliable biomarkers that provide information about the biological state of the cell. Recently, studies have described a number of metabolic pathway intermediates (called metabolites) associated with the development of Alzheimer's disease. To describe a summary of all the characteristic properties of metabolism, the term metabolome is used. The metabolome of exosomes could be a tool to understand the changes in the metabolism of Alzheimer's patients and to discover new biomarkers of the disease. My future research aims to characterize exosomes in Alzheimer's disease in the context of metabolism. First, I aim to identify proteins that are specifically present in exosomes from the CNS. This will allow an efficient and reliable isolation of exosomes from patient samples. Another goal is to characterize enzymes and metabolites present in exosomes from the CNS of Alzheimer’s disease patients. This may help to discover new biomarkers for Alzheimer's disease. Since exosomes are involved in the communication between cells, I would like to analyze the effect of the metabolome of exosomes on neurons. For this purpose, an in vitro model of Alzheimer's disease will be used, of which exosomes will be isolated and their metabolome will be analyzed. Neuronal cells will be treated with these exosomes and be analyzed. Thus, correlations between the metabolome of exosomes and their effect on neuronal cells can be drawn. In conclusion, this research project contributes to understand the importance of CNS exosomes in the occurrence and development of Alzheimer's disease from a metabolic point of view.

• DFG Programme: WBP Fellowship
• International Connection: Spain
• Host: Professor Dr. Juan Manuel Falcón-Pérez