Yu Yiru, Wang Zhen, Chai Zhen, Ma Shuyu, Li Ang, Li Ye
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710049, China.
Department of Periodontology, College of Stomatology, Xi'an Jiaotong University, Xi'an 710049, China.
Int J Mol Sci. 2025 Aug 26;26(17):8272. doi: 10.3390/ijms26178272.
Alzheimer's disease (AD) has emerged as a global health threat that demands early detection to seize the optimal intervention opportunity. Central nervous system (CNS)-derived extracellular vesicles (EVs), lipid-bilayer nanoparticles released by CNS cells, carry key biomolecules involved in AD pathology, positioning them as a promising source of biomarkers for early detection. Current breakthroughs in EV-based isolation and detection technologies have opened up the possibility of early, accurate AD diagnosis. This review summarizes their multifaceted roles in AD pathogenesis, including amyloid-β (Aβ) aggregation, tau propagation, neuroinflammation, and synaptic dysfunction, and highlights neuron- and glia-derived EV biomarkers with translational potential. We further outline recent advances in EV isolation techniques-including density-, size-, charge/dielectric-, immunoaffinity-, and acoustics-based approaches-and emerging detection platforms such as fluorescence, surface plasmon resonance (SPR), surface-enhanced Raman spectroscopy (SERS), electrochemical, and nanomechanical sensors for sensitive, multiplex AD diagnostics. Finally, we discuss key challenges, including standardization, sensitivity, and high-throughput adaptation, and explore future directions such as automated microfluidics and single-vesicle analysis. CNS-derived EVs hold significant promise as minimally invasive, next-generation tools for early AD detection and precision medicine.
阿尔茨海默病（AD）已成为一种全球健康威胁，需要早期检测以抓住最佳干预时机。中枢神经系统（CNS）衍生的细胞外囊泡（EVs）是由CNS细胞释放的脂质双层纳米颗粒，携带与AD病理相关的关键生物分子，使其成为早期检测中有前景的生物标志物来源。基于EV的分离和检测技术的当前突破为早期、准确的AD诊断开辟了可能性。本综述总结了它们在AD发病机制中的多方面作用，包括淀粉样β蛋白（Aβ）聚集、tau蛋白传播、神经炎症和突触功能障碍，并强调了具有转化潜力的神经元和胶质细胞衍生的EV生物标志物。我们进一步概述了EV分离技术的最新进展，包括基于密度、大小、电荷/介电、免疫亲和和声控的方法，以及新兴的检测平台，如用于灵敏、多重AD诊断的荧光、表面等离子体共振（SPR）、表面增强拉曼光谱（SERS）、电化学和纳米机械传感器。最后，我们讨论了关键挑战，包括标准化、灵敏度和高通量适配，并探索了未来方向，如自动化微流控和单囊泡分析。CNS衍生的EV作为早期AD检测和精准医学的微创下一代工具具有巨大潜力。
