Ishizawa K, Ksiezak-Reding H, Davies P, Delacourte A, Tiseo P, Yen S H, Dickson D W
Department of Pathology, Mayo Clinic Jacksonville, FL 32224, USA.
Acta Neuropathol. 2000 Sep;100(3):235-44. doi: 10.1007/s004019900177.
Neurofibrillary tangles (NFT), one of the histopathological hallmarks of Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), and Pick bodies in Pick's disease (PiD) are composed of microtubule-associated protein tau, which is the product of alternative splicing of a gene on chromosome 17. Alternative expression of exon 10 leads to formation of three- or four-repeat tau isoforms. To study the differential expression of exon 10, we performed double-labeling immunohistochemistry of the hippocampal formation in nine AD, four PSP and three PiD cases. Cryostat sections were processed with and without formic acid (FA) treatment, and double-stained with anti-tau (Alz-50 or PHF-1) or anti-amyloid P component antibodies and one of two specific anti-exon 10 antibodies (E-10). The effect of proteinase-K treatment was also evaluated. The results suggest the following. First, in AD, E-10 immunoreactivity is present in most intracellular NFT, but not in most dystrophic neurites and neuropil threads, suggesting differential expression of tau isoforms in specific cellular domains. Second, in AD, E-10 immunoreactivity is lost or blocked in most extracellular NFT, possibly due to proteolysis. Third, in PSP, E-10 immunoreactivity is hidden or blocked in NFT and tau-positive glial inclusions, but FA treatment exposes the epitope consistent with the hypothesis that PSP inclusions contain four-repeat tau. Fourth, E-10 immunoreactivity is present in dentate fascia NFT in AD and PSP, but not in Pick bodies in the dentate fascia or other areas. The results suggest that expression of exon 10 in tau is specific for cellular domains in a disease-specific manner.
神经原纤维缠结（NFT）是阿尔茨海默病（AD）和进行性核上性麻痹（PSP）的组织病理学特征之一，而Pick病（PiD）中的Pick小体是由微管相关蛋白tau组成，tau是17号染色体上一个基因可变剪接的产物。外显子10的可变表达导致三重复或四重复tau异构体的形成。为了研究外显子10的差异表达，我们对9例AD、4例PSP和3例PiD患者的海马结构进行了双重免疫组织化学染色。冰冻切片分别经过和不经过甲酸（FA）处理，并用抗tau（Alz-50或PHF-1）或抗淀粉样P成分抗体以及两种特异性抗外显子10抗体（E-10）之一进行双重染色。还评估了蛋白酶K处理的效果。结果表明如下。第一，在AD中，E-10免疫反应性存在于大多数细胞内NFT中，但不存在于大多数营养不良性神经突和神经毡丝中，提示tau异构体在特定细胞区域存在差异表达。第二，在AD中，大多数细胞外NFT中的E-10免疫反应性丧失或被阻断，可能是由于蛋白水解作用。第三，在PSP中，E-10免疫反应性在NFT和tau阳性胶质包涵体中被隐藏或阻断，但FA处理可暴露表位，这与PSP包涵体含有四重复tau的假说一致。第四，E-10免疫反应性存在于AD和PSP的齿状回NFT中，但不存在于齿状回或其他区域的Pick小体中。结果表明，tau中外显子10的表达以疾病特异性方式对细胞区域具有特异性。
