Abnormal accumulation of prion protein mRNA in muscle fibers of patients with sporadic inclusion-body myositis and hereditary inclusion- body myopathy

• Published in: The American journal of pathology Vol. 145; no. 6; pp. 1280 - 1284
• Main Authors: Sarkozi, E, Askanas, V, Engel, WK
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.12.1994; American Society for Investigative Pathology
• Subjects: Adult; Aged; Biological and medical sciences; Diseases of striated muscles. Neuromuscular diseases; Humans; Immunohistochemistry; In Situ Hybridization; Inclusion Bodies - ultrastructure; Medical sciences; Middle Aged; Muscle Fibers, Skeletal - metabolism; Muscular Diseases - metabolism; Muscular Diseases - pathology; Myositis - metabolism; Myositis - pathology; Neurology; Prions - genetics; Prions - metabolism; RNA, Messenger - metabolism; Human; Immunohistochemistry; Pathogenesis; In situ; Hybridization; Congenital disease; Pathology; Striated muscle disease; Messenger RNA; Reducing body myopathy; β Amyloid protein; Myositis; Prion; Inclusion body
• ISSN: 0002-9440; 1525-2191

Sporadic inclusion-body myositis is the most common progressive muscle disease of older patients. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6 to 10-nm fibrils, both resembling those of Alzheimer brain, and Congo-red positivity. Hereditary inclusion-body myopathy designates patients cytopathologically similar but without inflammation. In both muscle diseases, prion, and several proteins characteristic of Alzheimer brain--eg, beta-amyloid protein and hyperphosphorylated tau (which normally are expressed mainly in neurons), and apolipoprotein E--are abnormally accumulated in vacuolated muscle fibers, by unknown mechanisms. We now demonstrate in both muscle diseases that prion mRNA is strongly expressed in the vacuolated muscle fibers, which suggests that their accumulated prion protein results, at least partly, from increased gene expression. This, to our knowledge, is the first demonstration of abnormally increased prion mRNA in human disease. Another novel finding is the increased prion mRNA in human muscle macrophages, and both increased prion protein and prion mRNA in regenerating muscle fibers. The latter indicates that prion may play a role in human muscle development.