Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (10): 2982-2997.doi: 10.4103/NRR.NRR-D-23-01979

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Longitudinal assessment of peripheral organ metabolism and the gut microbiota in an APP/PS1 transgenic mouse model of Alzheimer’s disease

Hongli Li1, 2, Jianhua Huang3 , Di Zhao3 , Lemei Zhu4 , Zheyu Zhang1 , Min Yi1, *, Weijun Peng1, 2, *   

  1. 1 Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China;  2 National Clinical Research Center for Metabolic Diseases, Changsha, Hunan Province, China;  3 Hunan Academy of Chinese Medicine, Changsha, Hunan Province, China;  4 Academician Workstation, Changsha Medical University, Changsha, Hunan Province, China
  • Online:2025-10-15 Published:2025-02-09
  • Contact: Weijun Peng, PhD, pengweijun87@csu.edu.cn; Min Yi, PhD, yimin66@csu.edu.cn.
  • Supported by:
    This study was financially supported by the National Natural Science Foundation of China, No. 82374552 (to WP); the Science and Technology Innovation Program of Hunan Province, No. 2022RC1220 (to WP); the Natural Science Foundation of Hunan Province of China, Nos. 2020JJ4803 (to WP), 2022JJ40723 (to MY); and the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY).

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Abstract: Alzheimer’s disease not only affects the brain, but also induces metabolic dysfunction in peripheral organs and alters the gut microbiota. The aim of this study was to investigate systemic changes that occur in Alzheimer’s disease, in particular the association between changes in peripheral organ metabolism, changes in gut microbial composition, and Alzheimer’s disease development. To do this, we analyzed peripheral organ metabolism and the gut microbiota in amyloid precursor protein-presenilin 1 (APP/PS1) transgenic and control mice at 3, 6, 9, and 12 months of age. Twelve-month-old APP/PS1 mice exhibited cognitive impairment, Alzheimer’s disease–related brain changes, distinctive metabolic disturbances in peripheral organs and fecal samples (as detected by untargeted metabolomics sequencing), and substantial changes in gut microbial composition compared with younger APP/PS1 mice. Notably, a strong correlation emerged between the gut microbiota and kidney metabolism in APP/PS1 mice. These findings suggest that alterations in peripheral organ metabolism and the gut microbiota are closely related to Alzheimer’s disease development, indicating potential new directions for therapeutic strategies.

Key words: Alzheimer’s disease,  APP/PS1 mice,  brain–kidney axis,  gut microbiota,  heart–brain axis,  liver–brain axis,  lung–brain axis,  microbiota–gut–brain axis,  peripheral organ metabolism,  spleen–brain axis