A new diagnostic tool for brain disorders: extracellular vesicles derived from neuron, astrocyte, and oligodendrocyte

Brain disorders are the leading cause of disability worldwide, affecting people's quality of life and causing economic burdens. The current clinical diagnosis of brain disorders relies solely on individual phenotypes and lacks accurate molecular biomarkers. An emerging field of research centers around extracellular vesicles (EVs), nanoscale membrane vesicles which can easily cross the blood-brain barrier. EVs in the blood are derived from various tissues, including the brain. Therefore, purifying central nervous system (CNS)-derived EVs from the blood and analyzing their contents may be a relatively non-invasive way to analyze brain molecular alterations and identify biomarkers in brain disorders. Recently, methods for capturing neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in peripheral blood were reported. In this article, we provide an overview of the research history of EVs in the blood, specifically focusing on biomarker findings in six major brain disorders (Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, depression, and autism spectrum disorder). Additionally, we discuss the methodology employed for testing CNS-derived EVs. Among brain disorders, Alzheimer's disease has received the most extensive attention in EV research to date. Most studies focus on specific molecules, candidate proteins, or miRNAs. Notably, the most studied molecules implicated in the pathology of these diseases, such as Aβ, tau, and α-synuclein, exhibit good reproducibility. These findings suggest that CNS-derived EVs can serve as valuable tools for observing brain molecular changes minimally invasively. However, further analysis is necessary to understand the cargo composition of these EVs and improve isolation methods. Therefore, research efforts should prioritize the analysis of CNS-derived EVs' origin and genome-wide biomarker discovery studies.