Hayward P A, Bell J E, Ironside J W
University Department of Pathology, Western General Hospital, Edinburgh, UK.
Neuropathol Appl Neurobiol. 1994 Aug;20(4):375-83. doi: 10.1111/j.1365-2990.1994.tb00983.x.
Current criteria for the histological diagnosis of Creutzfeldt-Jakob disease (CJD) include features such as spongiform change, neuronal loss and reactive gliosis which are shared to a varying extent with other neuro-degenerative disorders. Reliable visualization of prion protein (PrP) has substantial potential value in diagnostic practice and as a research tool, since accumulation of the disease-associated isoform of this protein is apparently specific for spongiform encephalopathies. A number of antisera against PrP have previously been employed in conjunction with a range of pre-treatments designed to optimize the specificity of immunostaining; such varied usage makes the comparison and interpretation of results difficult. This study was undertaken to identify optimal combinations of each of three PrP antisera and five pre-treatments designed to specifically demonstrate disease-specific PrP in a series of seven CJD cases, six cases of Alzheimer-type dementia and six non-demented control cases. Specific staining of amyloid plaques, spongiform neuropil, neurons and, occasionally, astrocytes was achieved in CJD cases. Alzheimer and control cases were unstained. Use of formic acid with guanidine thiocyanate, and hydrolytic autoclaving with IB3 and SP30 antisera proved most effective and can be recommended for future immunocytochemical studies. PrP immunocytochemistry revealed a greater extent of subcortical neural involvement than routine histological techniques in CJD; the relationship between classical neuropathology in CJD and PrP accumulation as revealed by immunocytochemistry is not clear cut and requires further investigation. These findings may help to broaden our understanding of human spongiform encephalopathies, and have implications for diagnostic practices in neuropathology.
克雅氏病（CJD）组织学诊断的现行标准包括海绵状改变、神经元丢失和反应性胶质增生等特征，这些特征在不同程度上也见于其他神经退行性疾病。朊蛋白（PrP）的可靠可视化在诊断实践和作为研究工具方面具有很大的潜在价值，因为这种蛋白的疾病相关异构体的积累显然是海绵状脑病所特有的。此前已使用多种抗PrP血清，并结合一系列旨在优化免疫染色特异性的预处理方法；如此多样的用法使得结果的比较和解释变得困难。本研究旨在确定三种PrP抗血清与五种预处理方法的最佳组合，以在7例CJD病例、6例阿尔茨海默型痴呆病例和6例非痴呆对照病例中特异性显示疾病特异性PrP。在CJD病例中实现了淀粉样斑块、海绵状神经纤维、神经元以及偶尔的星形胶质细胞的特异性染色。阿尔茨海默病病例和对照病例均未染色。使用甲酸与硫氰酸胍，以及用IB3和SP30抗血清进行水解高压灭菌被证明是最有效的，可推荐用于未来的免疫细胞化学研究。PrP免疫细胞化学显示，与常规组织学技术相比，CJD病例中皮质下神经受累程度更大；免疫细胞化学显示的CJD经典神经病理学与PrP积累之间的关系并不明确，需要进一步研究。这些发现可能有助于拓宽我们对人类海绵状脑病的理解，并对神经病理学的诊断实践产生影响。
