From molecular signal to clinical solution: extracellular vesicles in precision medicine for neurodegenerative diseases

Neurodegenerative diseases continue to elude effective treatment because there are no tools available for detecting subclinical pathology, and therefore providing CNS-targeted interventions, prior to incompletely reversible neuronal loss. Extracellular vesicles (EVs), nanosized, membrane-delimited particles released by all cell types in the CNS, have emerged as highly promising therapeutic candidates to target the existing challenges in parallel. Their cell-type-specific molecular cargo is a faithful replicator of disease state and can be monitored at an early stage, longitudinally through time, and non-invasively across accessible biofluids. Additionally, native & bioengineered EVs surfaced-functionalized with CNS-targeting ligands can cross the blood-brain-barrier to impact neuroinflammation, promote clearance of tau, α-synuclein, TDP-43 and amyloid-β and deliver precision neurotherapeutics to defined cellular targets. This review highlights the role of EVs within a patient-specific theranostic framework that integrates multi-omics profiling, artificial intelligence-assisted cargo design, and real-time treatment monitoring to guide personalized therapeutic strategies. We also discuss the emerging potential of mitovesicles, compare EVs with other CNS drug-delivery platforms, and examine the key challenges to clinical translation, including standardization, large-scale manufacturing, and regulatory considerations in accordance with the MISEV2023 guidelines. Collectively, we propose EV-based theranostics as a promising precision medicine strategy with the potential to transform the diagnosis and treatment of neurodegenerative diseases.