Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood–brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. Researchers from University Medicine Göttingen discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer’s and Parkinson’s diseases. In the later part, they discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.
Potential outcomes of exosome-cargo investigations for neurodegenerative diseases
Identification and characterization of whole cargoes of bio-fluid-based exosomes (e.g., protein, RNA and DNA) isolated at different stages of the disease could not only provide potential novel diagnostic and prognostic markers, but also provide insights into the pathogenesis of these incurable neurodegenerative diseases