Study of the establishment of animal model with Alzheimer's disease to control thepathological aging

C型尼曼-皮克病（NPC）患者的神经病理学研究显示，在表现缓慢进展的慢性病程的病例中存在神经原纤维缠结（NFT）。然而，在20岁以下的鼻咽癌患者中没有发现NFT，并且已知10年或更长时间的神经细胞代谢的长期扰动可能导致NFT的形成。患有NPC的小鼠表现为常染色体隐性遗传，会出现肝脾肿大和共济失调、震颤等神经系统症状，并在14周龄左右死亡。这与人类NFT阳性鼻咽癌的时间尺度不可比较。本文采用LFB-Bodian染色、电镜和抗阿尔茨海默氏神经原纤维缠结（ANT, Ab39）抗体免疫组化对小鼠鼻鼻癌（spm/spm）进行神经病理学检查，探讨阿尔茨海默氏神经原纤维的变化。通过LBF-Bodian染色和市购抗phf -tau免疫染色，在11周和13周大的spm/spm的大脑皮层、海马回和中脑的神经细胞中可以在显微镜下看到类似NFT的神经原纤维变化。然而，只有来自新皮层的神经元才能被抗ANT （Ab39）抗体染色。同样，只有在新皮层神经元中才能看到成对的螺旋状丝。小鼠鼻咽癌新皮层中nft样结构的发现可能为阐明阿尔茨海默病的发病机制提供动物模型。我们也尝试建立新生spm脑神经元细胞培养，但尚未成功。

Neuropathological studies of patients with Niemann-Pick disease type C (NPC) have revealed neurofibrillary tangles (NFT) in cases showing slowly progressive chronic courses. However, no NFT have been noted in NPC patients younger that 20 years, and it is known that long-term perturbation of neuronal cellular metabolism for 10 years or more may result in NFT formatiion.Mice with NPC, which shows autosomal recessive inheritance, develop hepatosplenomegaly and neurological manifestations such as ataxia and tremor, and die at about 14 weeks of age. This is not comparable with the time scale of NFT positive NPC in humans. Here we examined murine NPC (spm/spm) neuropathologically, using LFB-Bodian staining , electron microscopy and immunohistochemistry with anti Alzheimer's neurofibrillary tangle (ANT, Ab39) antibody, in order to investigate Alzheimer's neurofibrillary changes.Neurofibrillary changes resembling NFT can be seen microscopically in neuranal cells of cerebral cortex, hippocampal gyrus and midbrain older at 11 and 13-week old spm/spm by LBF-Bodian staining and by immunostaining with commercially available anti-PHF-tau. However, only neuron from neocortex can be staind with anti ANT (Ab39) antibody. Equally, paired helical filaments only can be seen in the neuron of neocortex. The present findings of NFT-like structure in the neocortex of murine NPC may provide an animal model for elucidating the pathogenesis of Alzheimer's disease. We also tried to establish the neuronal cell culture from the brain of newborn spm, but have not been successful yet.