Rapid induction of intraneuronal neurofibrillary tangles in apolipoprotein E-deficient mice
Rapid induction of intraneuronal neurofibrillary tangles in apolipoprotein E-deficient mice
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DOI：
10.1073/pnas.151253098
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发表时间：
2001-07-17
影响因子：
11.1
通讯作者：
Lynch, G
中科院分区：
文献类型：
--
作者：
Bi, XN;Yong, AP;Lynch, G
将从载脂蛋白E缺陷小鼠制备的培养海马切片暴露于组织蛋白酶B和L的抑制剂，然后使用针对人配对螺旋丝的抗体进行免疫细胞化学处理。在海马CA1区的下托、皮层和齿状回的门区发现密集的AT8免疫阳性沉积物。这种分布与阿尔茨海默病中缠结的描述一致。标记结构的出现属于与先前提出的人类海马神经元内神经元缠结进展阶段相对应的类别。电子显微镜分析证实，微管破坏和扭曲的纤维束存在于受影响地区的神经元。这些结果支持这一假设，即部分溶酶体功能障碍是阿尔茨海默病的贡献者，并提出了一个简单的模型，用于研究疾病的重要组成部分。
Cultured hippocampal slices prepared from apolipoprotein E-deficient mice were exposed to an inhibitor of cathepsins B and L and then processed for immunocytochemistry using antibodies against human paired helical filaments. Dense, AT8-immunopositive deposits were found in the subiculum, stratum oriens of hippocampal field CA1, and the hilus of the dentate gyrus. This distribution agrees with that described for tangles in Alzheimer's disease. The appearance of the labeled structures fell into categories that correspond to previously proposed stages in the progression of intraneuronal neurofibrillary tangles in human hippocampus. Electron microscopic analyses confirmed that microtubule disruption and twisted bundles of filaments were present in neurons in the affected areas. These results support the hypothesis that partial lysosomal dysfunction is a contributor to Alzheimer's disease and suggest a simple model for studying an important component of the disease.