Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis

• Published in: The American journal of pathology Vol. 141; no. 1; pp. 31 - 36
• Main Authors: Askanas, V, Engel, WK, Alvarez, RB
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.07.1992; American Society for Investigative Pathology
• Subjects: Actin Cytoskeleton - ultrastructure; Adolescent; Adult; Aged; Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - metabolism; Biological and medical sciences; Biopsy; Child; Child, Preschool; Diseases of striated muscles. Neuromuscular diseases; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Inclusion Bodies - chemistry; Inclusion Bodies - metabolism; Inclusion Bodies - ultrastructure; Medical sciences; Microscopy, Electron; Middle Aged; Muscles - chemistry; Muscles - pathology; Muscles - ultrastructure; Myositis - metabolism; Myositis - pathology; Neurology; Human; Pathology; Nervous system diseases; Exploration; Myositis; Amyloid; Muscle
• ISSN: 0002-9440; 1525-2191

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.