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

作　　者：Hongli Li Jianhua Huang Di Zhao Lemei Zhu Zheyu Zhang Min Yi Weijun Peng 

机构地区：[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

出　　处：《Neural Regeneration Research》2025年第10期2982-2997,共16页中国神经再生研究（英文版）

基　　金：financially supported by the National Natural Science Foundation of China,No.823 74552 (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);the Scientific Research Launch Project for New Employees of the Second Xiangya Hospital of Central South University (to MY)

摘　　要：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.

关 键 词：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 

分 类 号：R749.16[医药卫生—神经病学与精神病学]