Endo-Lysosomal and Ubiquitin CSF Biomarker Discovery by solid-phase extraction and LC-MS/MS

Dysfunctional proteostasis is increasingly implicated in neurodegenerative diseases which is exemplified by an accumulation of protein aggregates in the brain in e.g. Alzheimer's and Parkinson's disease. In addition, in Alzheimer's disease there is an accumulation of autophagic vesicles within neurites. Susceptibility in Parkinson's disease has convincingly been connected with genetic mutations associated with lysosomal storage disorders. Proteostasis is maintained in the cell by the endo-lysosomal system, autophagy and the ubiquitin-proteasome system. Identifying biomarkers reflecting proteostasis might increase our understanding of neurodegenerative disorders and serve as tools to monitor the effects of new treatment strategies. To date no treatment has proven effective, neither in Alzheimer’s disease nor Parkinson’s disease. The aim of this project was to identify proteins involved in the endo-lysosomal system, autophagy and the ubiquitin-proteasome system in CSF. This information will be used to select and target relevant proteins for quantitative analysis using e.g. PRM or SRM to evaluate these proteins as potential biomarkers in neurodegenerative diseases.