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 cerebralβ-amyloid protein characteristics between 5xFAD transgenic mice and alzheimer's disease patients

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(amyloidβ-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<15μm的Aβ斑块占比最高;两者脑内相同面积中直径为[45,60)μm及≥60μm 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<15μm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≥60μm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<15μm、[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。

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