Focus on Extracellular Vesicles: Exosomes and Their Role in Protein Trafficking and Biomarker Potential in Alzheimer’s and Parkinson’s Disease

Abstract

Growing evidence indicates that small extracellular vesicles, called exosomes, are prominent mediators of neurodegenerative diseases such as prion, Alzheimer’s and Parkinson’s disease. Exosomes contain neurodegenerative disease associated proteins such as the prion protein, β-amyloid and α-synuclein. Only demonstrated so far in vivo with prion disease, exosomes are hypothesised to also facilitate the spread of β-amyloid and α-synuclein from their cells of origin to the extracellular environment. In the current review, we will discuss the role of exosomes in Alzheimer’s and Parkinson’s disease including their possible contribution to disease propagation and pathology and highlight their utility as a diagnostic in neurodegenerative disease.

Extracellular Vesicles: Unique Intercellular Delivery Vehicles

“…Since in many of these diseases the aggregating proteins are carried by EVs, EVs are considered to have a role in cell-to-cell transmission of the toxic proteins and (pre-)fibrils [129,130]). In prion-related diseases - the transmissible spongiform encephalopathies, beta-sheet conformations of prion protein (PrP SC ) can propagate and be transmitted between both cells and organisms [131].…”

Microvesicles as Vehicles for Tissue Regeneration: Changing of the Guards

“…Interestingly, they could both provide protection from neurodegeneration and have a central role in the propagation of neurotoxicity [59]. Exosomes have been implicated in spreading the key disease molecules of Parkinson’s and Alzheimer’s diseases through the brain [60], and MVs may also play a part in this important disease process. As far as their protective action is concerned, MSC-based therapies applied in numerous models of neurodegenerative disorders have provided strong evidence of paracrine regeneration effects [61].…”

Alzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers

“…Exosomes, small extracellular vesicles (20–120 nm in diameter) [58] developing from endosomes through multivesicular bodies, have recently emerged as key players in cellular communication and transport of molecules in both health and disease, including neuronal toxicity [33] and neurodegenerative disorders [59]. Exosomes can carry different cargos such as proteins, RNA and miRNA and can also contain monomeric Aß, tau and α-synuclein [12, 17, 46, 59] and can propagate tau pathology [4].…”

“…Exosomes can carry different cargos such as proteins, RNA and miRNA and can also contain monomeric Aß, tau and α-synuclein [12, 17, 46, 59] and can propagate tau pathology [4]. Thus, exosomes could potentially also carry aggregated proteins such as oAß.…”