5xFAD转基因小鼠与阿尔茨海默病患者大脑中β-淀粉样蛋白特征的异同

doi:10.3969/j.issn.1006-7795.2022.01.018

首都医科大学学报 ›› 2022, Vol. 43 ›› Issue (1): 106-112.doi: 10.3969/j.issn.1006-7795.2022.01.018

5xFAD转基因小鼠与阿尔茨海默病患者大脑中β-淀粉样蛋白特征的异同

孟霞¹, 李梦¹, 王晶晶¹, 张静^1,2,3, 陈柏安^1,2,3*, 卢静^1,2,3

1.首都医科大学实验动物部,北京 100069;
2.首都医科大学基础医学院实验动物学学系,北京 100069;
3.首都医科大学基础医学院神经再生修复研究北京市重点实验室,北京 100069

收稿日期:2021-09-01 出版日期:2022-02-21 发布日期:2022-01-27
基金资助:
北京市科技新星计划(Z191100001119056),北京市老年病医疗研究中心项目(PXM2019_026283_000003)。

Similarities and differences of cerebral β-amyloid protein characteristics between 5xFAD transgenic mice and alzheimer's disease patients

Meng Xia¹, Li Meng¹, Wang Jingjing¹, Zhang Jing^1,2,3, Chen Baian^1,2,3*, Lu Jing^1,2,3

1. Laboratory Animal Resource Center, Capital Medical University, Beijing 100069, China;
2. Department of Laboratory Animal Sciences, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
3. School of Basic Medical Sciences, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing100069, China

Received:2021-09-01 Online:2022-02-21 Published:2022-01-27
Contact: * E-mail:baianchen@ccmu.edu.cn
Supported by:
Beijing Nova Program of Science and Technology (Z191100001119056), Beijing Municipal Commission of Health and Family Planning (PXM2019_026283_000003).

摘要/Abstract

摘要： 目的探明5xFAD转基因小鼠与阿尔茨海默病(Alzheimer disease,AD)患者大脑中β-淀粉样蛋白(amyloid β-protein,Aβ)斑块特征的异同。方法利用免疫荧光染色通过单克隆抗体(4G8)检测了5xFAD转基因小鼠与AD患者大脑中的Aβ斑块,利用CaseViewer和GraphPad Prism 8软件对其脑内Aβ斑块进行定性定量分析,比较5xFAD转基因小鼠与AD患者大脑中Aβ斑块在形态、数量、类型等特征上的异同。结果 5xFAD转基因小鼠与AD患者大脑中Aβ斑块特征的主要相同点包括:在两者的大脑皮质和海马区中均可见明显的Aβ斑块;两者均可见弥散型Aβ斑块和致密型Aβ斑块;两者脑内均以直径<15 μm的Aβ斑块占比最高;两者脑内相同面积中直径为[45,60)μm及≥60 μm Aβ斑块的数量相似;两者脑内均可见明显的淀粉样脑血管病变(cerebral amyloid angiopathy,CAA)。5xFAD转基因小鼠与AD患者大脑中Aβ斑块特征的主要不同点包括:在5xFAD转基因小鼠脑内直径<15 μm的Aβ斑块显著少于AD患者脑内相同面积中的Aβ斑块(P<0.001);而直径在[15,30)μm、[30,45)μm的Aβ斑块显著多于AD患者脑内相同面积中的Aβ斑块(P=0.001, P=0.020);此外,在AD患者脑内致密型Aβ斑块中可见有典型日冕结构的Aβ斑块,而5xFAD转基因小鼠脑内未见典型日冕结构的Aβ斑块。结论 5xFAD转基因小鼠大脑中Aβ斑块出现的位置、主要形态、相同面积中直径为[45,60)μm及≥60 μm以上Aβ斑块数量以及CAA等方面的特征与我国AD患者高度相似,但是在大脑相同面积中直径<15 μm、[15,30)μm、[30,45)μm的Aβ斑块数量以及在有无典型日冕结构Aβ斑块等方面的特征与我国AD患者不同,明确以上特征是使用5xFAD转基因小鼠研究我国AD患者相关病变特征的重要前提。

关键词: 阿尔茨海默病, β-淀粉样蛋白, Aβ斑块, 5xFAD转基因小鼠, 阿尔茨海默病患者

Abstract: Objective To explore the relationship between 5xfad transgenic mice and Alzheimer's disease similarities and differences amyloid β-protein (Aβ) plaque characteristics. Methods Immunofluorescence staining was used to detect Aβ plaques in the brain of 5xFAD transgenic mice and Alzheimer's disease (AD) patients by monoclonal antibody (4G8). The qualitative and quantitative analysis of Aβ plaques in the brain of 5xFAD transgenic mice and AD patients was conducted by CaseViewer software, and the similarities and differences in the morphology, quantity and type of Aβ plaques in the brain of 5xFAD transgenic mice and AD patients were compared Results The main similarities between the characteristics of Aβ plaques in the brain of 5xFAD transgenic mice and AD patients were as follows: obvious Aβ plaques were found in the cerebral cortex and hippocampus of both mice and AD patients; Diffused Aβ plaques and dense Aβ plaques were observed in both of them. The proportion of Aβ plaques with A diameter of <15 μm was the highest in both brain regions. The number of Aβ plaques at [45,60)μm and ≥60 μm in the same brain area was similar between the two groups. Both have obvious cerebral amyloid angiopathy (CAA) in their brains. The main differences in the characteristics of Aβ plaques in the brains of 5xFAD transgenic mice and AD patients were as follows: Aβ plaques with A diameter of <15 μm in the brains of 5xFAD transgenic mice were significantly less than Aβ plaques of the same area in the brains of AD patients (P<0.001); Aβ plaques with diameters of [15,30)μm and [30,45)μm were significantly higher than those with the same area in AD patients (P=0.001, P=0.020); In addition, Aβ plaques with typical coronal structure were observed in the dense Aβ plaques in AD patients, but not in 5xFAD transgenic mice. Conclusion The location, main morphology of Aβ plaques, number of Aβ plaques with diameter of [45,60) μm and ≥60 μm in the same area and characteristics of CAA are highly similar to the AD patient; however, the number of Aβ plaques with a diameter of <15 μm, [15,30)μm and[30,45)μm in the same area of the brain, and the characteristics of Aβ plaque with or without typical coronal structure are different from those of AD patients.

Key words: Alzheimer's disease (AD), β-amyloid protein (Aβ), Aβ plaque, 5xFAD transgenic mice, AD patients

中图分类号:

R743

孟霞, 李梦, 王晶晶, 张静, 陈柏安, 卢静. 5xFAD转基因小鼠与阿尔茨海默病患者大脑中β-淀粉样蛋白特征的异同[J]. 首都医科大学学报, 2022, 43(1): 106-112.

Meng Xia, Li Meng, Wang Jingjing, Zhang Jing, Chen Baian, Lu Jing. Similarities and differences of cerebral β-amyloid protein characteristics between 5xFAD transgenic mice and alzheimer's disease patients[J]. Journal of Capital Medical University, 2022, 43(1): 106-112.

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5xFAD转基因小鼠与阿尔茨海默病患者大脑中β-淀粉样蛋白特征的异同

Similarities and differences of cerebral β-amyloid protein characteristics between 5xFAD transgenic mice and alzheimer's disease patients

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