Proteomic comparison between CSF samples and CSF‐derived EVs from patients with Alzheimer’s disease, Parkinson’s disease and Lewy Body dementia

Abstract

AbstractBackgroundExtracellular vesicles (EVs) have recently been considered as a potential biomarker source for a variety of diseases, including neurodegenerative disorders. EVs are important mediators of intercellular communication due to their capacity to transfer genetic material, lipids and proteins. By means of their communication role, interesting biomarkers are often enriched in EVs compared to total biofluid. In this study, this hypothesis is tested as untargeted proteomics is performed on both CSF samples and CSF‐derived EV samples from the same cohort with different dementia diseases.MethodCSF samples were collected from 297 patients (with Alzheimer’s disease (AD), Parkinson’s disease (PD), PD with cognitive deficit (PDCD), PD with dementia (PDD), Lewy Body dementia (LBD)) and healthy controls (HC). Furthermore, EVs were obtained from 500µL of the same CSF samples, isolated by SmartSEC HT. Total protein quantification was measured using absorbance at 280nm for CSF samples, and by fluorescence (NanoOrangeTM) for CSF‐derived EV samples. For both types of sample, LC‐MS/MS based proteomics analyses were performed.ResultTotal protein quantification showed multiple significant differences between all groups, both in CSF samples and in CSF‐derived EV samples. In both types of sample, PDCD group showed the highest protein concentration after normalization. In regard to LC‐MS/MS results, a first analysis resulted in a total of 3036 identified proteins (1564 protein groups) for the CSF samples, and 6627 proteins (3360 protein groups) for the CSF‐derived EV samples. The current analyses show four statistically differentially expressed proteins between CSF‐derived EV samples from HC and AD, AD and PD, LBD and PDCD. By the time of AAIC2023, also CSF samples will be analysed and a comparison will be drawn between both types of sample.ConclusionAs more in‐depth proteomic analyses will be performed by AAIC2023, a definite conclusion will be given at the conference. For now, already differences in total protein concentration were observed between the different disease groups and LC‐MS/MS of CSF‐derived EV samples resulted in four statistically differentially expressed proteins.