摘要：

目的 评价P62蛋白在临床常见神经变性病特征性病理改变中的表达变化，探讨其病理诊断意义。方法 收集1994年6月至2017年10月经临床和病理明确诊断的神经变性病脑组织标本共 11例，包括阿尔茨海默病5例（其中2例合并嗜银颗粒病）、帕金森病3例、进行性核上性麻痹2例、多系统萎缩1例；另以3例无神经变性病的脑组织标本为对照。分别进行HE、卢卡斯快蓝及Gallyas-Braak银染，以及β-淀粉样蛋白、AT8、α-突触核蛋白和P62抗体免疫组织化学染色，显微镜下观察不同神经变性病的特征性病理改变和P62蛋白表达变化。结果 阿尔茨海默病神经原纤维缠结、帕金森病路易小体和路易轴索、进行性核上性麻痹丛状星形细胞、嗜银颗粒病的嗜银颗粒，以及多系统萎缩少突胶质细胞内包涵体均表达P62蛋白，且形态特征与其特异性抗体染色结果相一致；另外，阿尔茨海默病神经炎性斑仅少量表达P62蛋白，而弥散斑表达阴性；淀粉样小体P62蛋白表达亦呈阳性；正常对照脑组织不表达P62蛋白。结论 P62蛋白在阿尔茨海默病、帕金森病、进行性核上性麻痹、多系统萎缩等疾病特征性病理改变和淀粉样小体中均表达阳性，且形态与各种神经变性病组织学及相应特异性蛋白表达结果一致，推荐P62抗体作为神经变性病的辅助病理诊断。

关键词: 神经变性疾病, 衔接蛋白质类, 信号转导, 自噬, 免疫组织化学, 病理学

Abstract:

Objective To evaluate the expression of P62 protein in the characteristic pathological changes of common neurodegenerative diseases and to explore its significance in pathological diagnosis. Methods Eleven cases of neurodegenerative diseases and 3 normal controls which were clinically and pathologically diagnosed from June 1994 to October 2017 were included. The neurodegenerative diseases consisted of 5 cases of Alzheimer's disease (AD) and 2 of which were diagnosed as AD combined with argyrophilic grain disease (AGD), 3 cases of Parkinson's disease (PD), 2 cases of progressive supranuclear palsy (PSP) and 1 case of multiple system atrophy (MSA). Three cases without neurological symptoms, signs and brain pathological changes were used as the normal control. Brain tissues were stained with HE, luxol fast blue (LFB) and Gallyas-Braak silver staining, as well as antibodies to amyloid β-protein (Aβ), AT8, α-synuclein and P62. The staining results were compared under microscope. Results P62 protein was present in the neurofibrillary tangles of AD, in the Lewy body and Lewy neurites of PD, in the tufted astrocyte of PSP, in the argyrophilic grain of AGD and in the glial cytoplasmic inclusion of MSA. The morphological characteristics were consistent with the results of staining with specific antibodies. P62 protein was only expressed in a small amount in the neuritic plaque of AD, and the diffuse plaques were negative. In addition, P62 protein was also deposited in corpora amylacea. No positive pathological structure of P62 immunohistochemical staining was found in normal control brain tissues. Conclusions The P62 protein is expressed in the characteristic pathological changes and corpora amylacea of AD, PD, PSP, MSA and other diseases. Morphological staining results are consistent with histology of various neurodegenerative diseases and corresponding specific protein expression staining results. So the P62 antibody is recommended as the aiding pathological diagnosis of neurodegenerative diseases.

Key words: Neurodegenerative diseases, Adaptor proteins, signal transducing, Autophagy, Immunohistochemistry, Pathology