Insights Into the Proteomic Profiling of Extracellular Vesicles for the Identification of Early Biomarkers of Neurodegeneration

Extracellular vesicles (EVs) are involved in the development and progression of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Moreover, EVs have the capacity to modify the physiology of neuronal circuits by transferring proteins, RNA, lipids, and metabolites. The proteomic characterization of EVs (exosomes and microvesicles) from preclinical models and patient samples has the potential to reveal new proteins and molecular networks that affect the normal physiology prior to the appearance of traditional biomarkers of neurodegeneration. Noteworthy, many of the genetic risks associated to the development of Alzheimer’s and Parkinson’s disease affect the crosstalk between mitochondria, endosomes, and lysosomes. Recent research has focused on determining the role of endolysosomal trafficking in the onset of neurodegenerative diseases. Proteomic studies indicate an alteration of biogenesis and molecular content of EVs as a result of endolysosomal and autophagic dysfunction. Researchers from the National Institute of Genomic Medicine, Mexico City discuss the status of EV proteomic characterization and their usefulness in discovering new biomarkers for the differential diagnosis of neurodegenerative diseases. Despite the challenges related to the failure to follow a standard isolation protocol and their implementation for a clinical setting, the analysis of EV proteomes has revealed the presence of key proteins with post-translational modifications that can be measured in peripheral fluids.

Protein signature of EVs in Parkinson’s and Alzheimer’s disease

The schematic representation shows a compilation of changes in the protein content of EVs under pathological conditions. The proteins/genes were classified by groups: Parkinson’s disease (PD, blue boxes), Alzheimer’s disease (AD, green boxes), and endolysosomal pathway-related proteins or structural components of EVs (red boxes). The color-coding of protein names follows the same classification criteria.