Tai Chi-induced exosomal LRP1 is associated with memory and hippocampus plasticity in aMCI patients

Objectives The study was designed to identify the potential peripheral processes of circulating exosome in response to TC exercise and the possibility of its loaded cargos in mediating the effects of TC training on cognitive function among older adults with amnestic mild cognitive impairment (aMCI). Design, setting, and participants This was a multi-center randomized controlled trial. One hundred community-dwelling old adults with aMCI were randomly assigned (1:1) to experimental (n=50) and control groups (n=50). Intervention The experimental group participated in TC exercise 5 times/week, with each session lasting 60min for 12 weeks. Both experimental and control groups received health education every 4 weeks. Measurements The primary outcome was global cognitive function. Neurocognitive assessments, MRI examination, and large-scale proteomics analysis of peripheric exosome were conducted at baseline and after 12-week training. Outcome assessors and statisticians were blinded to group allocation. Results A total of 96 participants (96%) completed all outcome measurements. TC training improved global cognitive function (adjusted mean difference [MD]=1.9, 95%CI 0.93 to 2.87, p<0.001) and memory (adjusted MD=6.42, 95%CI 2.09 to 10.74, p=0.004), increased right hippocampus volume (adjusted MD=90.39, 95%CI 20.09 to 160.69, p=0.012), and enhanced rest state functional connectivity (rsFC) between hippocampus and cuneus, which mediated the group effect on global cognitive function (bootstrapping CIs: [0.0208, 1.2826], [0.0689, 1.2211]) and verbal delay recall (bootstrapping CI: [0.0002, 0.6277]). Simultaneously, 24 differentially expressed exosomal proteins were detected in tandem mass tag-labelling proteomic analysis. Of which, the candidate protein low-density lipoprotein receptor-related protein 1 (LRP1) was further confirmed by parallel reaction monitoring and ELISA. Moreover, the up-regulated LRP1 was both positively associated with verbal delay recall and rsFC (left hippocampus-right cuneus). Conclusion TC promotes LRP1 release via exosome, which was associated with enhanced memory function and hippocampus plasticity in aMCI patients. Our findings provided an insight into potential therapeutic neurobiological targets focusing on peripheric exosome in respond to TC exercise.