Biography

Neuropathology studies support that, in Alzheimer’s Disease (AD), blood-brain barrier (BBB) dysfunction is detectable before cognitive decline and/or other brain pathologies and may contribute to dementia and motor symptoms. We newly reported that, compared with control patient exosomes (Control-Exos), circulating Alzheimer’s Disease patient exosomes (AD-Exos) can induce barrier dysfunction in recipient brain microvascular endothelial cells (BMECs), in a manner dependent on RNA-cargos at a dose of 1,000 particles/cell. Our study provides a potential mechanism by which these exosomes contribute to pathogenesis and disease progression of AD. Yet, exosomal functional small non-coding RNAs (sncRNAs) remain to be identified in the context of AD. A growing number of reports have established that many, if not all, effects of exosomes are mediated by two major sncRNA cargos, microRNAs (miRs) or tRNA fragments (tRFs). Microvasculopathy-related sncRNAs are a family of sncRNAs were reported to directly target microvascular endothelial cells. We reported that the miR23a-27a-24 cluster, miR30b, and novel sncRNA tRFGly and tRFVal are microvasculopathy-related sncRNAs in contexts of infections and inflammation. Using stem-loop qPCR, which is a common method for detecting sncRNAs in extracellular vesicles, we measured vasculopathy-related miR125, miR23a cluster, miR30b, tRFGly, tRFVal, and irrelevant U6 snRNA in AD- vs. Control-Exos, and observed upregulated miR23a and miR30b in AD-Exos. Furthermore, Control-Exos had been enriched with designed sncRNA mimics or antisense oligonucleotides (ASOs) (1 pmol/1x108 particles) using an approach reported. Using our established Fluidic Atomic Force Microscope (AFM)-based single living cell approaches, we observed that miR23a-ASO-enriched Control-Exos ameliorated AD-Exo-induced recipient BMEC dysfunction by protection on the lateral binding forces among BMECs. These data collectively suggest that targeting specific exosomal sncRNAs stabilizes the BBB in AD. Thus, we have obtained important preliminary data for seeking a new avenue to protect the BBB in AD.