文献类型：期刊文献

英文题名：Porcine plasma-derived extracellular vesicles orchestrate multi-target neuroimmune reconfiguration to alleviate Alzheimer's disease pathology in a 5×FAD mouse model

作者：Lu, Xiaoyang[1];Jiang, Yiling[1];Lin, Xiuqing[1];Zhang, Yuanxing[1];Liu, Qin[1];Chen, Shouwen[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2026

卷号：23

期号：1

外文期刊名：JOURNAL OF NEUROINFLAMMATION

收录：;Scopus(收录号：2-s2.0-105044043539);WOS:【SCI-EXPANDED(收录号:WOS:001814015200002)】；

基金：This work was supported by the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism grant 2021 Sci & Tech 03-28 (Shanghai Municipal Education Commission), the ECUST-OPM Open Fund (20220701), and the Fundamental Research Funds for the Central Universities (222201251732).

语种：英文

外文关键词：Alzheimer's disease; Small extracellular vesicles; Porcine plasma; Microglia; Reactive astrocyte; Neuroinflammation; Cross-species therapy

摘要：Background Systemic factors found in young blood possess the capacity to revitalize the aging brain, yet the clinical translation of human-derived therapeutics is severely limited by donor scarcity. We hypothesized that porcine plasma-derived small extracellular vesicles (PpSEVs) could serve as a scalable, cross-species alternative by leveraging evolutionarily conserved bioactive cargoes.Results In this study, we demonstrate that PpSEVs efficiently penetrate the blood-brain barrier and show relative enrichment in the hippocampus CA3 region of 5 & times;FAD mice. Transcriptomic profiling and functional assays reveal that PpSEVs reverse AD pathology by reconfiguring the dysregulated neuroimmune network rather than through broad immune suppression. Specifically, PpSEVs exert a dual-action effect on microglia by blocking caspase-1/GSDMD axis-mediated pyroptosis, while simultaneously enhancing CD68-dependent amyloid-beta clearance. This microglial modulation occurs in tandem with the reprogramming of reactive astrocytes, characterized by the downregulation of neurotoxic C3 and the upregulation of neuroprotective S100A10. Furthermore, we identify a direct, glia-independent neurotrophic pathway in which PpSEVs activate neuronal BDNF signaling to rescue synaptic integrity and cognitive function.Conclusions By demonstrating robust cross-species efficacy without provoking immunotoxicity, our study positions PpSEVs as a potent, multi-target intervention that decouples therapeutic benefits from human donor reliance, paving the way for sustainable, xenogeneic exosome-based AD therapies.