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阿尔茨海默病APP/PS1转基因小鼠模型中外周器官代谢和肠道微生物群的纵向评估。

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

作者信息

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

机构信息

Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

National Clinical Research Center for Metabolic Diseases, Changsha, Hunan Province, China.

出版信息

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

DOI:10.4103/NRR.NRR-D-23-01979
PMID:39610107
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11826447/
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.

摘要

《阿尔茨海默病杂志》/nrgr/04.03/01300535 - 202510000 - 00028/图1/v/2024 - 11 - 26T163120Z/图像 - 标签图像文件格式 阿尔茨海默病不仅影响大脑，还会诱发外周器官的代谢功能障碍并改变肠道微生物群。本研究的目的是调查阿尔茨海默病中发生的全身变化，特别是外周器官代谢变化、肠道微生物组成变化与阿尔茨海默病发展之间的关联。为此，我们分析了3、6、9和12月龄的淀粉样前体蛋白 - 早老素1（APP/PS1）转基因小鼠和对照小鼠的外周器官代谢及肠道微生物群。与年轻的APP/PS1小鼠相比，12月龄的APP/PS1小鼠表现出认知障碍、与阿尔茨海默病相关的大脑变化、外周器官和粪便样本中的独特代谢紊乱（通过非靶向代谢组学测序检测）以及肠道微生物组成的显著变化。值得注意的是，APP/PS1小鼠的肠道微生物群与肾脏代谢之间出现了强相关性。这些发现表明，外周器官代谢和肠道微生物群的改变与阿尔茨海默病的发展密切相关，为治疗策略指明了潜在的新方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/678d5966be28/NRR-20-2982-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/ad219cdf020f/NRR-20-2982-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/faaf7f6cae99/NRR-20-2982-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/460d352087d8/NRR-20-2982-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/a24555729b22/NRR-20-2982-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/ec2e9dcae9bc/NRR-20-2982-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/5890fea1bdbb/NRR-20-2982-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/fbc87745d88c/NRR-20-2982-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/678d5966be28/NRR-20-2982-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/ad219cdf020f/NRR-20-2982-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/faaf7f6cae99/NRR-20-2982-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/460d352087d8/NRR-20-2982-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/a24555729b22/NRR-20-2982-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/ec2e9dcae9bc/NRR-20-2982-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/5890fea1bdbb/NRR-20-2982-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/fbc87745d88c/NRR-20-2982-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e0a/11826447/678d5966be28/NRR-20-2982-g009.jpg

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