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

对C型尼曼-皮克病(NPC)患者的神经病理学研究表明，慢性进展缓慢的患者会出现神经原纤维缠结(NFT)。然而，在20岁以下的鼻咽癌患者中未发现NFT，已知10年或更长时间神经细胞代谢的长期扰动可能导致NFT的形成。鼻咽癌表现为常染色体隐性遗传，出现肝脾肿大和神经症状，如共济失调和震颤，约14周龄死亡。这与人类NFT阳性鼻咽癌的时间尺度是不可比的。为了研究阿尔茨海默病的神经纤维变化，我们用LFB-Bodian染色、电子显微镜和抗阿尔茨海默病神经纤维缠结(ANT，AB39)抗体免疫组织化学方法对小鼠鼻咽癌(SPM/SPM)进行了神经病理学检查。然而，只有来自新皮质的神经元才能被抗ANT(AB39)抗体染色。同样，成对的螺旋细丝仅见于新皮质神经元。目前在小鼠鼻咽癌新皮质中发现的NFT样结构可能为阐明阿尔茨海默病的发病机制提供了动物模型。我们也曾尝试建立新生SPM的神经细胞培养方法，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.