Utility of extracellular vesicles in the diagnosis of central nervous system diseases

Abstract

Central nervous system (CNS) disorders encompass a diverse spectrum of conditions characterized by intricate pathological mechanisms, and the presence of the blood–brain barrier (BBB) has long impeded early diagnosis. Extracellular vesicles (EVs) are lipid bilayer nanoparticles released by living cells that can encapsulate and transport bioactive molecules such as proteins and nucleic acids across the BBB. EVs can be detected in biofluids such as blood and cerebrospinal fluid (CSF) through non-invasive or minimally invasive assays, and have emerged as highly promising vehicles for CNS liquid biopsies. Recent studies demonstrate that specific EV-associated protein cargoes (e.g., phosphorylated tau, α-syn) and non-coding RNAs (e.g., miR-422a, miR-409-3p) exhibit distinct differential expression profiles across various pathologies. These molecular signatures hold promise for early detection, differential diagnosis, and disease staging, with some biomarker panels showing high diagnostic accuracy. However, whether they outperform conventional CSF biomarkers still requires direct comparison and validation within the same cohorts. This review highlights recent research advances in the use of EVs for the diagnosis of Alzheimer’s disease and Parkinson’s disease, briefly touches upon other CNS disorders including stroke, glioma, multiple sclerosis, Huntington’s disease, and amyotrophic lateral sclerosis, and discusses the clinical translational potential and remaining challenges of EV-based diagnostics.