Tai Chi-Induced Exosomal LRP1 is Associated With Memory Function and Hippocampus Plasticity in aMCI Patients

Author: Miaoran Lin1, Weilin Liu1, Chuyi Ma1, Jiahui Gao2, Li Huang2, Jingfang Zhu2, Shengxiang Liang2, Youze He2, Jiao Liu1, Jing Tao3, Zhizhen Liu2, Jia Huang3, Zhifu Wang4, Lidian Chen5
1 The Institute of Rehabilitation Industry (ML, WL, CM, JL, LC), Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
2 Rehabilitation Medical Technology Joint National Local Engineering Research Center (JG, LH, JZ, SL, YH, ZL), Fuzhou 350122, China.
3 TCM Rehabilitation Research Center of SATCM (JT, JH), Fuzhou 350122, China.
4 The Affiliated Rehabilitation Hospital (ZW), Fujian University of Traditional Chinese Medicine, Fuzhou 350003, China.
5 The Institute of Rehabilitation Industry (ML, WL, CM, JL, LC), Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; Fujian University of Traditional Chinese Medicine (LC), Shangjie University Town, Fuzhou, China. Electronic address: cld@fjtcm.edu.cn.
Conference/Journal: Am J Geriatr Psychiatry
Date published: 2024 Apr 26
Other: Pages: S1064-7481(24)00321-X , Special Notes: doi: 10.1016/j.jagp.2024.04.012. , Word Count: 310

The study was designed to identify the potential peripheral processes of circulating exosome in response to Tai Chi (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 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.

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).

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.

Keywords: Tai chi; amnestic mild cognitive impairment; circulating exosome; cognitive function; hippocampus plasticity.

PMID: 38824049 DOI: 10.1016/j.jagp.2024.04.012