Raman spectroscopy reveals biochemical differences in plasma derived extracellular vesicles from sporadic amyotrophic lateral sclerosis patients

Abstract Sporadic Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease for which there is no validated blood based biomarker. Extracellular vesicles (EVs) have the potential to solve this unmet clinical need. However, due to their heterogeneity and complex chemical composition, EVs are difficult to study. Raman spectroscopy (RS) is an optical method that seems particularly well suited to address this task. In fact, RS provides an overview of the biochemical composition of EVs quickly and virtually without any sample preparation. In this work, we studied by RS small extracellular vesicles (sEVs), large extracellular vesicles (lEVs) and blood plasma of sporadic ALS patients and of a matched cohort of healthy controls. The obtained results highlighted lEVs as a particularly promising biomarker for ALS. In fact, their Raman spectra show that sporadic ALS patients have a different lipid content and less intense bands relative to the aromatic aminoacid phenylalanine.