C型Niemann-Pick病神经原纤维缠结的形成与特征

The characteristics of neurofibrillary tangles in brains of patients with Niemann-Pick disease type C

目的探讨C型尼曼-皮克病（NPC）脑部神经原纤维缠结（NFT）形成的时相特征。方法以17例年龄7个月至55岁的NPC患者为研究对象，采用tau蛋白和有丝分裂期相关抗体进行免疫组织化学染色和银染，分析患者脑内NFT形成的特点。结果最早可在4岁的患者海马旁回发现典型的NFT形成，随年龄增长数量逐渐增多。在形态上与阿尔茨海默病（AD）所见高度相似，但未发现老年斑。在NPC中，有丝分裂期磷酸化表位早于tau蛋白过度磷酸化及NFT形成。结论NFT形成并非老龄化过程的结果，且与老年斑的存在与否并无关联。cdc2／cyclinB1可能是NFT形成的关键性早期事件，针对其活性的抑制剂对于早期干预NPC NFT的形成有重要意义。

Objective To describe the spatial and temporal characteristics of neurofibrillary tangles （NFT） in brains of patients with Niemann-Pick disease type C （NPC）. Methods In order to analyze formation of NFT in NPC, the brains collected from 17 patients with NPC aged from 7 months to 55 years old were investigated using antibodies against the protein tau and the specific proteins in mitotic phase. Results Typical NFT could be detected in the parahippocampus of a NPC patient as early as at 4 years old. The number of NFT were increasing along with the time. Gradually, the hippocampus and other regions of the temporal lobes and the frontal lobes would be affected with the time. Immunohistochemically, the NFT formed the shape similar to NFT seen in AD brains, without the presence of senile plagues. Interestingly, mitosis-phase markers appeared in the degenerating NPC neurons prior to hyperphosphorylation of tau and formation of NFT. Condusions The formation of NFT does not result from aging, for there is no close relation between the presence of senile plagues and the formation of NFT. Ectopic activation of ode2/ cyclinB1 kinase complex might be an early event leading to NFT formation. Antagonist of the kinase complex may potentially slow down the formation of NFT.