Unlocking the potential of circulating small extracellular vesicles in neurodegenerative disease through targeted biomarkers and advancements in biosensing.

Neurodegenerative diseases (NDDs) gradually affect neurons impacting both their function and structure, and they afflict millions worldwide. Detecting these conditions before symptoms arise is crucial for better prognosis and duality of life, given that the disease processes often begin years earlier. Yet, reliable and affordable methods to diagnose NDDs in these stages are currently lacking. There's a growing interest in using circulating extracellular vesicles (EVs), like small EVs (sEVs) also known as exosomes, as potential sources of markers for screening, diagnosing, and monitoring NDDs. This interest stems from evidence showing that these EVs can carry brain pathological proteins implicated in NDD pathology, and they can even traverse the blood-brain barrier. This review focuses on the creation of EVs, particularly sEVs with a size of less than 200 nanometers, methods for isolating sEVs, and recent advancements in biosensor development to detect NDD-related markers found in sEVs. Furthermore, it explores the potential of sEVs in diagnosing four major NDDs: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple system atrophy (MSA).