Proteomics analysis of pathological brain tissue in Parkinson's disease (PD) is of great importance to understand the molecular aetiology of degeneration and to develop curative treatments. To date, published studies have been restricted to the analysis of human post-mortem tissue samples, frequently derived from advanced disease stage and potentially altered by several factors. In this project we took advantage of the temporary access to PD patient's brain during electrode implantation to obtain in vivo molecular information from cerebral tissue at earlier stage of the disease. We further developed a dedicated tool to improve our tissue harvesting approach, and validated its efficiency and non-lesion effects in vivo in monkeys. This work opens the way to the proteomic analysis of fresh human brain samples to elucidate molecular causes of degeneration in PD. However such tissue investigation approach remains invasive and cannot be used in routine clinical screening for PD diagnosis. Proteomics analysis of cerebrospinal fluid (CSF) constitutes a promising alternative to identify neuropathological diagnosis markers. For this purpose, we developed a nanoparticle-assisted strategy enabling the enrichment of CSF proteins detection by mass spectrometry. Reproducibility and high throughput potentiality of our approach demonstrate its compatibility with clinical proteomics for PD diagnosis biomarker research in CSF. We also demonstrated the interest of this NP strategy for plasma and red blood cells proteome analysis. Finally, we evaluated the ability to use these NPs for in vivo protein harvesting in blood.
