Extracellular vesicles in neurodegenerative diseases: insights into peripheral–central crosstalk and therapeutic potential

Neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and cognitive impairment (CI), pose major challenges to global public health due to their high prevalence, disability, and mortality rates. Traditional neurobiology considers the central nervous system (CNS) as a relatively independent regulatory unit; however, recent studies have confirmed that the CNS forms a dynamically integrated network with the peripheral immune system, gut microbiota, and circulatory system. In this context, small extracellular vesicles (EVs) act as key mediators of intercellular communication, facilitating multidirectional signal exchange between peripheral organs and the CNS. By transporting bioactive molecules such as proteins, nucleic acids, and lipids, EVs establish a precise "molecular dialogue" that influences neuroinflammation, synaptic plasticity, and pathological protein propagation, thereby participating in the development and progression of NDs. This review systematically summarizes recent advances in the understanding of sEV-mediated peripheral–central crosstalk, highlights their diagnostic and therapeutic potential, and provides new perspectives for developing innovative interventions for NDs.