Askanas V, Engel W K, Bilak M, Alvarez R B, Selkoe D J
Department of Neurology, University of Southern California School of Medicine, Los Angeles.
Am J Pathol. 1994 Jan;144(1):177-87.
We immunostained muscle biopsies of 8 patients with sporadic inclusion body myositis (S-IBM), 7 patients with autosomal recessive hereditary inclusion body myopathy (H-IBM) (both diseases being characterized by similar muscle fiber vacuoles containing inclusions), and 11 normal and disease controls. We used the following well-characterized antibodies against tau protein: Tau-1, Alz-50, and anti-paired helical filament (PHF) antiserum. By light microscopy, in all S-IBM muscle biopsies virtually all vacuoles immunoreactive for ubiquitin and beta-amyloid protein also contained inclusions immunoreactive with Alz-50 and anti-PHF antiserum. With tau-1 antibody, strong immunoreactivity in the vacuoles was obtained only after dephosphorylation of muscle sections. By electronmicroscopy, all three antibodies immunodecorated exclusively cytoplasmic twisted tubulofilaments (TTFs). In H-IBM, virtually all ubiquitin and beta-amyloid-positive muscle fiber vacuoles contained inclusions immunoreactive with anti-PHF antiserum, but in only 40% of those fibers were the inclusions immunoreactive with Alz-50. In six H-IBM patients there were no tau-1 immunoreactive inclusions in any of their vacuolated muscle fibers; in one patient, 24% of the vacuolated fibers had tau-1 immunoreactivity. By demonstrating that hyperphosphorylated tau, which is characteristic of Alzheimer brain PHFs, is a component of S-IBM-muscle TTFs (which are also ultrastructurally similar to PHFs), our study: 1) provides the first demonstration of abnormally accumulated tau in nonneural tissue and 2) suggests that the cytopathogenesis in Alzheimer brain and S-IBM muscle may share some similar mechanisms. Whether the difference in tau immunoreactivity between S-IBM and most of the H-IBM patients reflects a difference in genetically determined transcriptional or posttranslational modifications of tau protein or other factors remains to be determined.
我们对8例散发性包涵体肌炎（S-IBM）患者、7例常染色体隐性遗传性包涵体肌病（H-IBM）患者（这两种疾病的特征均为肌纤维出现含有包涵体的类似空泡）以及11名正常对照和疾病对照的肌肉活检样本进行了免疫染色。我们使用了以下针对tau蛋白的特性明确的抗体：Tau-1、Alz-50以及抗双螺旋丝（PHF）抗血清。通过光学显微镜观察，在所有S-IBM肌肉活检样本中，几乎所有对泛素和β-淀粉样蛋白呈免疫反应性的空泡也含有与Alz-50和抗PHF抗血清呈免疫反应性的包涵体。使用tau-1抗体时，只有在肌肉切片去磷酸化后，空泡中才会出现强免疫反应性。通过电子显微镜观察，所有这三种抗体仅对细胞质扭曲微管丝（TTF）进行免疫标记。在H-IBM中，几乎所有泛素和β-淀粉样蛋白阳性的肌纤维空泡都含有与抗PHF抗血清呈免疫反应性的包涵体，但只有40%的这些纤维中的包涵体与Alz-50呈免疫反应性。在6例H-IBM患者中，其任何空泡化肌纤维中均无tau-1免疫反应性包涵体；在1例患者中，24%的空泡化纤维具有tau-1免疫反应性。通过证明阿尔茨海默病脑PHF的特征性高磷酸化tau是S-IBM肌肉TTF的一个组成部分（其在超微结构上也与PHF相似），我们的研究：1）首次证明了tau在非神经组织中的异常积聚；2）表明阿尔茨海默病脑和S-IBM肌肉中的细胞发病机制可能有一些相似的机制。S-IBM与大多数H-IBM患者之间tau免疫反应性的差异是否反映了tau蛋白在基因决定的转录或翻译后修饰方面的差异或其他因素，仍有待确定。
