Beyond the neuron: Exosomes as intercellular modulators of mitochondrial networks in the pathogenesis and treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by β-amyloid deposition, hyperphosphorylated tau protein, and progressive neuronal loss. Mitochondria form a dynamic interconnected network within the central nervous system, and their dysfunction plays a central role in AD, involving oxidative stress, kinetic dysregulation, and impaired mitochondrial autophagy. As key mediators of intercellular communication, exosomes carry bioactive components that regulate mitochondrial function in recipient cells. This review summarizes advances in research on exosomes as coordinators of the mitochondrial network in the central nervous system, regulating mitochondrial quality control across different neuronal cell types. It systematically outlines the molecular mechanisms by which exosomes modulate mitochondrial function in AD through regulating mitochondrial biogenesis, fusion-fission dynamics, mitochondrial autophagy, and related signaling pathways. Furthermore, it explores the potential of engineered exosome-based targeted therapies for AD intervention, aiming to provide a theoretical foundation and research direction for developing novel therapeutic strategies targeting mitochondrial dysfunction.