TY - JOUR AU - Wu, Ailin AU - Zeng, Yan AU - Huang, Yilin AU - Chen, Legao AU - Guo, Shunyuan AU - Wang, Jianwei AU - Mou, Xiaozhou AU - Chang, Xiaoru TI - Extracellular vesicles for Alzheimer's disease therapy: mechanisms, engineering strategies, and clinical translation JO - Extracellular Vesicles and Circulating Nucleic Acids PY - 2026 VL - 7 IS - 3 SP - 1158 EP - 88 SN - ISSN 2767-6641 (Online) AB -

Alzheimer's disease (AD), a progressive neurodegenerative disorder, remains a major global health challenge owing to its complex pathogenesis and the presence of the blood-brain barrier (BBB), which substantially limits the delivery of effective therapeutics to the brain. Extracellular vesicles (EVs), which exhibit favorable biocompatibility, low immunogenicity, and an intrinsic capacity to cross the BBB, have emerged as promising therapeutic agents and delivery platforms for AD. This review focuses on the therapeutic potential of EV-based interventions in AD and summarizes recent advances in EV-mediated modulation of AD-related pathological processes, including amyloid-β (Aβ) clearance, tau protein regulation, neuroinflammation suppression, oxidative stress attenuation, and synaptic repair. Although EV-based therapies offer notable advantages, such as targeted BBB penetration and reduced immunogenic responses, their clinical translation remains constrained by safety concerns, including off-target effects, dose-dependent toxicity, and potential disturbances in neuroplasticity. In addition, this review discusses EV engineering strategies aimed at regulating the gut-brain axis (GBA), enhancing brain targeting, and advancing clinical translation. EV-based therapeutic interventions should therefore be developed within a safety-oriented framework supported by rigorous short- and long-term toxicological evaluation. Overall, this review highlights the therapeutic promise of EVs for AD while underscoring the need for rational engineering, standardized characterization, and safety-centered translational strategies to ensure clinical feasibility.

KW - Alzheimer's disease KW - extracellular vesicles KW - MISEV2023 KW - engineering KW - clinical translation KW - gut-brain axis KW - intranasal delivery DO - 10.20517/evcna.2026.43 UR - https://dx.doi.org/10.20517/evcna.2026.43