Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis.
Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis.
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发表时间：
1992-07
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通讯作者：
V. Askanas;W. Engel;R. B. Alvarez
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作者：
V. Askanas;W. Engel;R. B. Alvarez
在11例包涵体肌炎（IBM）患者中的11例，包括1例遗传性病例，空泡化肌纤维含有大的和多个小的包涵体，对β -淀粉样蛋白（β AP）具有免疫反应。所有的IBM肌肉活检组织在电子显微镜下都有特征性的细胞质小管细丝（CTFs）。14例对照肌肉活检均未发现IBM特征的β AP免疫反应性（IR）包涵体。在光镜水平上，β AP-IR包涵体与泛素免疫反应性共定位。通过免疫金电子显微镜，β AP免疫反应性定位于a)无定形，模糊结构，b)密集的絮状物质，c)直径6-8 nm的松散排列的淀粉样原纤维簇，d)直径6-8 nm的模糊松散原纤维结构。β AP免疫反应性结构通常接近CTFs，但CTFs本身不含β AP- ir。我们的研究首次证明了- AP在异常的人类肌肉中积累。这一发现提示，除了阿尔茨海默病、唐氏综合征和荷兰型遗传性脑血管淀粉样变性外，β AP可能在其他疾病的发病机制中发挥重要作用，包括中枢神经系统外的疾病，例如IBM。
In 11 of 11 inclusion-body myositis (IBM) patients, including one hereditary case, vacuolated muscle fibers contained large and multiple small inclusions immunoreactive for beta-amyloid protein (beta AP). All IBM muscle biopsies had characteristic cytoplasmic tubulo-filaments (CTFs) by electron microscopy. None of 14 control muscle biopsies contained the beta AP immunoreactive (IR) inclusions characteristic of IBM. On the light microscopy level, beta AP-IR inclusions colocalized with ubiquitin immunoreactivity. By immunogold electronmicroscopy, beta AP immunoreactivity was localized to a) amorphous, poorly defined structures, b) dense floccular material, c) clusters of loosely packed amyloidlike fibrils 6-8 nm in diameter, and d) poorly defined loose fibrillar structures 6-8 nm in diameter. beta AP immunoreactive structures were often in proximity to CTFs, but CTFs themselves never contained beta AP-IR. Our study provides the first demonstration of beta AP accumulations in abnormal human muscle. This finding suggests that in addition to Alzheimer's disease, Down syndrome, and Dutch-type hereditary cerebrovascular amyloidosis, beta AP may play an important role in the pathogenesis of other diseases, including ones outside the central nervous system, for example, IBM.