Key points are not available for this paper at this time.
Abstract Background Neuroinflammation represents a prevalent pathological characteristic of Alzheimer’s disease (AD). Research indicates that peripheral immune cells, such as activated macrophages, contribute to the pathogenesis of neurodegenerative diseases by triggering neuroinflammatory processes. This suggests that the interaction between immune cells of the peripheral and central nervous systems (CNS) plays a pivotal role in the advancement of AD. Exosomes are recognized as vital mediators facilitating communication between peripheral and CNS immune cells. However, the specific role of peripherally activated macrophages in accelerating AD progression via exosomal pathways remains unresolved. Methods The study employed in vivo and in vitro assays to identify the role of exosomes derived from activated macrophages (M1 macrophages). Methods such as single-cell sequencing, RT-PCR, flow cytometry, western blot, and immunofluorescence were utilized to elucidate how exosomes regulate the interaction between M1 macrophages and CNS immune cells. Results The experimental results initially showed that exosomes derived from M1 macrophages (M1-EXO) were primarily engulfed by microglia both in vitro and in vivo. Subsequent validation indicated that M1-EXO induces the formation of disease inflammatory microglia (DIM), accelerates Aβ accumulation, and contributes to cognitive impairment. Moreover, it was confirmed that exosomal miR-155-5p from M1 macrophages induced DIM formation by reducing SOCS1 expression and activating phosphorylation of the JAK1/STAT1 signaling pathway. Conclusion These findings reveal a communication mechanism between peripheral M1 macrophages and central microglia in the metastatic microenvironment mediated by exosomes, affecting the pathological progression of AD. The study also provides theoretical evidence demonstrating a potential mechanism by which M1 macrophages accelerate the progression of AD.
Yan et al. (Fri,) studied this question.