This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

Novel Findings Provide Insight Into Nature of Filaments

Jerry R. Mendell, MD; Zarife Sahenk, MD; Tracy Gales, MS; Laura Paul

Arch Neurol. 1991;48(12):1229-1234.

Abstract
• Inclusion body myositis (IBM) represents a serious debilitating disease of muscle without identifiable cause or treatment. Muscle biopsy specimens have characteristic rimmed vacuoles, varying degrees of inflammation, and, most importantly, cytoplasmic and intranuclear filamentous inclusions of unknown composition. Fresh-frozen sections of muscle biopsy specimens from 24 IBM cases were stained with Congo red dye (pH, 10.5 to 11.0). Control biopsy specimens included polymyositis, dermatomyositis, hereditary vacuolar myopathies of unknown cause, acid maltase deficiency, distal myopathy, oculopharyngeal dystrophy, and chloroquine myopathy. Sections were also immunostained with antibody to transthyretin, human P component, and immunoglobulin light chains. In the vacuolated fibers in IBM, amyloidogenic green-birefringent deposits were seen. Some deposits were delicate and wispy appearing, and others were plaque-like. The size of deposits varied, measuring 1 x 2 to 8 µm, and rarely up to 20 µm in length. The number of amyloid-positive fibers correlated with the number of vacuolated fibers. Similar deposits were seen in one case of distal myopathy and one hereditary vacuolar myopathy. Other control cases were negative for amyloid deposits. Antibody staining for known amyloidogenic proteins was negative. This study demonstrates that the filaments in IBM share properties with amyloid proteins. The location implies that this amyloid material is formed intracellularly, rather than having a systemic derivation. The association of amyloid deposits with autophagic vacuoles in IBM raises the likely possibility that the filaments represent a modification of a normal protein within an acidic degradative vacuolar compartment. An alternative possibility, considering the shared properties of IBM filaments and prions (which include size and amyloidogenic properties), is that IBM represents a human prion disease. Further studies will be required to resolve the nature of the amyloidogenic filaments in IBM, but these findings may provide clues to the pathogenesis of this poorly understood disorder. In addition, the findings should facilitate the clinical diagnosis of IBM.

Author Affiliations
From the Division of Neuromuscular Disease, Department of Neurology, College of Medicine, The Ohio State University, Columbus.

Footnotes
Accepted for publication July 17, 1991.

Reprint requests to Room 463, Means Hall, The Ohio State University, 1654 Upham Dr, Columbus, OH 43210 (Dr Mendell).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Inclusion body myositis: old and new concepts
Amato and Barohn
J. Neurol. Neurosurg. Psychiatry 2009;80:1186-1193.
ABSTRACT | FULL TEXT  

How citation distortions create unfounded authority: analysis of a citation network
Greenberg
BMJ 2009;339:b2680-b2680.
ABSTRACT | FULL TEXT  

Rabbits fed cholesterol-enriched diets exhibit pathological features of inclusion body myositis
Chen et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008;294:R829-R835.
ABSTRACT | FULL TEXT  

Correlation of muscle biopsy, clinical course, and outcome in PM and sporadic IBM
Chahin and Engel
Neurology 2008;70:418-424.
ABSTRACT | FULL TEXT  

Inducible overexpression of wild-type prion protein in the muscles leads to a primary myopathy in transgenic mice
Huang et al.
Proc. Natl. Acad. Sci. USA 2007;104:6800-6805.
ABSTRACT | FULL TEXT  

Genetically Augmenting A{beta}42 Levels in Skeletal Muscle Exacerbates Inclusion Body Myositis-Like Pathology and Motor Deficits in Transgenic Mice
Kitazawa et al.
Am. J. Pathol. 2006;168:1986-1997.
ABSTRACT | FULL TEXT  

Unicorns, dragons, polymyositis, and other mythical beasts
Askanas et al.
Neurology 2004;63:403-404.
FULL TEXT  

Polymyositis: An Ongoing Discussion About a Disease Entity
Bronner et al.
Arch Neurol 2004;61:132-135.
ABSTRACT | FULL TEXT  

Inclusion body myositis evolving in systemic lupus erythrematosus? A case report
Massawi et al.
Rheumatology (Oxford) 2003;42:1012-1014.
FULL TEXT  

Randomized pilot trial of {beta}INF1a (Avonex) in patients with inclusion body myositis
Neurology 2001;57:1566-1570.
ABSTRACT | FULL TEXT  

Inclusion Body Myositis Mimicking Motor Neuron Disease
Dabby et al.
Arch Neurol 2001;58:1253-1256.
ABSTRACT | FULL TEXT  

Progress in inflammatory myopathies: good but not good enough
DALAKAS
J. Neurol. Neurosurg. Psychiatry 2001;70:569-573.
FULL TEXT  

Paired Helical Filaments of Inclusion-Body Myositis Muscle Contain RNA and Survival Motor Neuron Protein
Broccolini et al.
Am. J. Pathol. 2000;156:1151-1155.
ABSTRACT | FULL TEXT  

{alpha}B-Crystallin immunolocalization yields new insights into inclusion body myositis
Banwell and Engel
Neurology 2000;54:1033-1041.
ABSTRACT | FULL TEXT  

Synergistic effect of {beta}-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells
Baron et al.
Brain 2000;123:374-379.
ABSTRACT | FULL TEXT  

Cultured inclusion-body myositis muscle fibers do not accumulate {beta}-amyloid precursor protein and can be innervated
McFerrin et al.
Neurology 1999;53:2184-2184.
ABSTRACT | FULL TEXT  

Does Overexpression of ßAPP in Aging Muscle Have a Pathogenic Role and a Relevance to Alzheimer's Disease? : Clues from Inclusion Body Myositis, Cultured Human Muscle, and Transgenic Mice
Askanas and Engel
Am. J. Pathol. 1998;153:1673-1677.
FULL TEXT  

Transgenic Mice Over-Expressing the C-99 Fragment of ßPP with an {alpha}-Secretase Site Mutation Develop a Myopathy Similar to Human Inclusion Body Myositis
Jin et al.
Am. J. Pathol. 1998;153:1679-1686.
ABSTRACT | FULL TEXT  

Amyloid-ß Deposition in Skeletal Muscle of Transgenic Mice : Possible Model of Inclusion Body Myopathy
Fukuchi et al.
Am. J. Pathol. 1998;153:1687-1693.
ABSTRACT | FULL TEXT  

Sporadic Inclusion-Body Myositis and Hereditary Inclusion-Body Myopathies: Diseases of Oxidative Stress and Aging?
Askanas and Engel
Arch Neurol 1998;55:915-920.
FULL TEXT  

Myoblast Transfer in the Treatment of Duchenne's Muscular Dystrophy
Mendell et al.
NEJM 1995;333:832-838.
ABSTRACT | FULL TEXT