Tai Chi-Induced Exosomal LRP1 is Associated with Memory Function and Hippocampal Plasticity in aMCI Patients

Background:

Exercise, including Tai Chi (TC) was beneficial for cognitive function of older adults with aMCI. However, the underlying molecular mechanism of TC on neuroprotection remains largely unknown. Exercise-released exosomes have been identified as novel mediators of cell-to-cell communication, playing a significant role in regulating hippocampal synaptic plasticity and nerve regeneration, as evidenced by ex vivo trials. No previous studies were done to address the gap in understanding the relationship between exercise-induced exosome, therapeutically hippocampus plasticity, and neurocognitive function response to TC training by using proteomics technology. 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).

Methods:

This was a multicenter 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). The experimental group participated in TC exercise 5 times/week, with each session lasting 60 minutes for 12 weeks. Both experimental and control groups received health education every 4 weeks. 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 0.93-2.87, p <0.001) and memory (adjusted MD = 6.42, 95%CI 2.09-10.74, p = 0.004), increased right hippocampus volume (adjusted MD = 88.52, 95%CI 13.63 -163.4, p = 0.021), 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).

Conclusions:

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.

Dr. Miaoran Lin is a faculty member at Fujian Medical University. She joined the research group of Prof. Chen at Fujian University of Traditional Chinese Medicine and received her PhD degree in Rehabilitation. Dr. Lin's work is dedicated to the prevention, intervention, and health management of neurological and brain disorders in older adults and primarily focuses on the role of exercise in cognitive protection. She is also committed to uncovering the mechanisms underlying the cognitive benefits of exercise through neuroimaging and molecular biology approaches. She has been actively involved in multiple national scientific programs and led several research projects aimed at promoting brain health.