中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (6): 2543-2552.doi: 10.4103/NRR.NRR-D-24-00975

• 原著:退行性病与再生 • 上一篇    下一篇

阿尔茨海默病小鼠不同脑区脂质代谢和甾醇谱解析

  

  • 出版日期:2026-06-15 发布日期:2026-04-18

Lipidomic and sterolomic profiles of different brain regions in the mouse model of Alzheimer’s disease

Xingsen Zhao1, 2, #, Liqun Chen3, #, Liangjian Ma4, Xiaohui Liu5, Zhongkai Cao1, Xiangjun Chen6, *, Lidan Hu1, *   

  1. 1Department of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang Province, China; 
    2Institute of Biotechnology, Xianghu Laboratory, Hangzhou, Zhejiang Province, China; 
    3Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin, China; 
    4The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, China; 
    5Metabolomics and Lipidomics Center of Tsinghua University, Beijing, China; 
    6Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
  • Online:2026-06-15 Published:2026-04-18
  • Contact: Lidan Hu, PhD, hulidan1@duke-nus.edu.sg; Xiangjun Chen, PhD, chenxiangjun@zju.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82200784, 32271311 and Qizhen Foundation, No. 226‐2023‐00008 (all to LH).

摘要: 阿尔茨海默病(AD)是痴呆最常见的原因。越来越多的证据表明,脂质代谢失调与阿尔茨海默病密切相关。然而,阿尔茨海默病中大脑脂质和甾醇变化的整体情况仍不明确。此次实验提取32周龄雄性5XFAD双转基因小鼠(突变型APP和PS1基因)和同龄野生型小鼠脑组织,利用非靶向脂质组学和固醇组学技术,探讨了小脑、海马和嗅球等脑区的脂质和固醇代谢谱。结果发现,阿尔茨海默病小鼠各脑区中各种脂质都发生了显著变化,尤其是在海马和嗅球中。这些变化表明这些脑区的能量水平发生了变化。进一步通路分析表明,关键代谢过程受到了显著干扰,包括与脂肪酸和细胞膜成分相关的代谢过程。研究还发现,参与脂质和甾醇调节的基因活性显著下降。这些发现为脂质和甾醇失衡如何导致阿尔茨海默病提供了新的见解,并指出了参与疾病进展的潜在代谢通路。


https://orcid.org/0000-0002-1145-2745 (Lidan Hu); https://orcid.org/0000-0003-0766-3416 (Xiangjun Chen)


关键词: 阿尔茨海默病, 胆固醇/生物合成, 胆固醇/代谢, 血脂异常, 脑脂质, 神经退行性疾病, 脂质代谢, 代谢, 阿尔茨海默病小鼠模型, 甾醇

Abstract: Alzheimer’s disease is the most common cause of dementia. Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease, the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear. In this study, we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice, which carry mutations in the amyloid precursor protein (APP) and presenilin 1 (PS1) genes. Using untargeted lipidomics and sterolomics techniques, we investigated the metabolic profiles of lipids, with a focus on sterols specifically, in three brain regions: cerebellum, hippocampus, and olfactory bulb. Our results revealed significant alterations in various lipids, particularly in the hippocampus and olfactory bulb, suggesting changes in energy levels in these regions. Further pathway analysis indicated notable disruptions in key metabolic processes, particularly those related to fatty acids and cell membrane components. Additionally, we observed decreased expression of 15 genes involved in lipid and sterol regulation. Collectively, these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease, highlighting potential metabolic pathways involved in the development of this debilitating disease.

Key words: Alzheimer’s disease, Alzheimer’s disease mouse model, brain lipids, dyslipidemias, lipidomic, metabolism, neurodegenerative disease, sterol