Extracellular vesicle-based biosensors for Alzheimer's disease: A new frontier in precision diagnostics

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, remains a diagnostic challenge due to its asymptomatic early stages and the lack of reliable, non-invasive biomarkers. Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-sized membrane-bound particles released by cells into biological fluids and have emerged as promising carriers of disease-specific biomarkers. These vesicles reflect the physiological and pathological state of their parental cells, encapsulating proteins, lipids, and nucleic acids relevant to AD pathology, such as amyloid-β, tau, and microRNAs. Recent advances in biosensor technology have enabled the development of highly sensitive and specific platforms to detect EV-associated biomarkers. Integrating EVs with biosensing approaches-ranging from electrochemical and optical sensors to nanomaterial-based systems-represents a promising strategy for early AD diagnosis, monitoring disease progression, and evaluating therapeutic efficacy. However, these technologies remain largely in preclinical or early translational stages, with further validation required in large-scale clinical cohorts. This review provides a comprehensive overview of the recent progress in EV-based biosensor technologies, highlighting their analytical performance, detection principles, and clinical relevance in AD diagnostics. Furthermore, we discuss the current challenges, such as standardization in EV isolation and characterization, and propose future perspectives for translating these innovative diagnostic tools into clinical practice. The integration of EV biology with advanced biosensing technologies represents an emerging advancement with strong potential for precision medicine in AD, although clinical translation will require rigorous validation and standardization.