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

Hongli Li; Jianhua Huang; Di Zhao; Lemei Zhu; Zheyu Zhang; Min Yi; Weijun Peng

doi:10.4103/NRR.NRR-D-23-01979

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

Neural Regen Res. 2025 Oct 1;20(10):2982-2997. doi: 10.4103/NRR.NRR-D-23-01979. Epub 2024 Jun 26.

Authors

Hongli Li^{1

2}, Jianhua Huang³, Di Zhao³, Lemei Zhu⁴, Zheyu Zhang¹, Min Yi¹, Weijun Peng^{1

2}

Affiliations

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.

PMID: 39610107
DOI: 10.4103/NRR.NRR-D-23-01979

Abstract

JOURNAL/nrgr/04.03/01300535-202510000-00028/figure1/v/2024-11-26T163120Z/r/image-tiff 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.