Cambon K, Davies H A, Stewart M G
The Open University, Department of Biological Sciences, Walton Hall, MK7 6AA, Milton Keynes, UK.
Neuroscience. 2000;97(4):685-92. doi: 10.1016/s0306-4522(00)00065-8.
To investigate the relationship between the three isoforms of apolipoprotein E (E2, E3 and E4) and the integrity of the synaptic circuitry in the dentate gyrus of the hippocampus, we have estimated the synapse per neuron ratio and mean apposition zone area per synapse at the electron microscope level in the dentate gyrus of apolipoprotein E knockout and human apolipoprotein E transgenic mice aged six to 24months. During ageing, only in human apolipoprotein E4 mice was there a decrease in synapse per neuron ratio, accompanied by an increase in synaptic size. When these mice were compared with human apolipoprotein E2, apolipoprotein E knockout and wild-type mice at old age, they displayed the lowest synapse per neuron ratio, but similar apposition zone area. In contrast, as in our previous study, aged apolipoprotein E knockout mice did not show any sign of synaptic degeneration. The functional consequences of such morphological changes remain to be determined. However, if such age-related loss of synapses occurred in the brain of Alzheimer apolipoprotein E4 patients, they might be additive to pathological processes and could contribute to greater cognitive impairment.
为了研究载脂蛋白E的三种异构体（E2、E3和E4）与海马齿状回突触回路完整性之间的关系，我们在电子显微镜水平上估算了6至24月龄的载脂蛋白E基因敲除小鼠和人载脂蛋白E转基因小鼠齿状回中每个神经元的突触比率以及每个突触的平均贴附区面积。在衰老过程中，仅在人载脂蛋白E4小鼠中每个神经元的突触比率下降，同时突触大小增加。当将这些小鼠与老年的人载脂蛋白E2小鼠、载脂蛋白E基因敲除小鼠和野生型小鼠进行比较时，它们显示出最低的每个神经元的突触比率，但贴附区面积相似。相比之下，正如我们之前的研究一样，衰老的载脂蛋白E基因敲除小鼠未显示出任何突触退化的迹象。这种形态学变化的功能后果仍有待确定。然而，如果在阿尔茨海默病载脂蛋白E4患者的大脑中发生这种与年龄相关的突触丧失，它们可能会叠加到病理过程中，并可能导致更严重的认知障碍。
