Inclusion-body myositis, a multifactorial muscle disease associated with aging: current concepts of pathogenesis

  title={Inclusion-body myositis, a multifactorial muscle disease associated with aging: current concepts of pathogenesis},
  author={Valerie Askanas and W. King Engel},
  journal={Current Opinion in Rheumatology},
  • V. Askanas, W. Engel
  • Published 1 November 2007
  • Biology, Medicine
  • Current Opinion in Rheumatology
Purpose of reviewSporadic inclusion-body myositis, the most common muscle disease of older persons, has no known cause or persistently beneficial treatment. The unfolding pathogenesis could lead to new treatment strategies and it is now of growing interest among clinicians and basic scientists. About 100 papers related to the subject were published in 2006 and the first part of 2007 (we cite only articles most relevant to this review). Recent findingsThis review focuses on the current concepts… 
Inclusion body myositis: new insights into pathogenesis
Understanding the paradoxes in sporadic inclusion body myositis is important in determining rational therapy for the disease.
Inclusion-body myositis in the elderly: an update
Recent advances in understanding the disease pathology are highlighted, and how to identify promising candidate molecules for future clinical trials are highlighted.
Inclusion body myositis: old and new concepts
Inclusion body myositis (IBM) is the most common idiopathic inflammatory myopathy occurring in patients over the age of 50 years and probably accounts for about 30% of all inflammatory myopathies.
Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains
Diagnostic criteria is summarized, and it is suggested that the intra-muscle-fiber degenerative component plays the primary role, leading to muscle-Fiber destruction and clinical weakness, since anti-inflammatory treatments are not of sustained benefit.
Investigating novel therapeutic approaches for sporadic inclusion body myositis (sIBM)
The results of this Thesis show that β-APP over-expression in vitro recapitulates many of the characteristic features of sIBM and can be used successfully to screen potential therapies.
Synaptic defects associated with s-inclusion body myositis are prevented by copper
The results suggest that Aβ-oligomers are the toxic Aβ species that trigger neuromuscular junction dysfunction.
Inflammatory myopathies: disease mechanisms
  • S. Greenberg
  • Biology, Medicine
    Current opinion in neurology
  • 2009
Clarification of disease mechanisms is providing a basis for rational drug development for some patients with myositis, and the identification and further characterization of the type 1 interferon pathway in dermatomyositis is leading down a path of genomic medicine.
Chapter 5 Inclusion Body Myositis
Inclusion body myositis is an insidious, slowly progressive myopathy of middle-aged and older individuals that is marked by the presence of rimmed vacuoles, inclusions, and an inflammatory infiltrate largely made up of CD8 T lymphocytes and macrophages.


Inclusion-body myositis
It is proposed that the identified abnormal accumulation, misfolding, and aggregation of proteins, perhaps provoked by the aging milieu and aggravated by the oxidative stress, lead to the s-IBM-specific vacuolar degeneration and atrophy of muscle fibers.
Proposed pathogenetic cascade of inclusion-body myositis: importance of amyloid-&bgr;, misfolded proteins, predisposing genes, and aging
This article summarizes the most recent findings leading to better understanding of the players in the pathogenetic cascade and suggests that lymphocytic inflammatory component is probably secondary, and it may contribute only slightly to muscle fiber damage in sporadic inclusion-body myositis.
Inclusion‐Body Myositis: Newest Concepts of Pathogenesis and Relation to Aging and Alzheimer Disease
  • W. Engel
  • Biology
    Journal of neuropathology and experimental neurology
  • 2001
Evidence is provided supporting the hypothesis that overexpression of AβPP within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade, and the remarkable pathologic similarities between s-IBM muscle and Alzheimer disease (AD) brain are discussed.
Sporadic inclusion body myositis—diagnosis, pathogenesis and therapeutic strategies
  • M. Dalakas
  • Biology, Medicine
    Nature Clinical Practice Neurology
  • 2006
Emerging data imply that continuous upregulation of cytokines and major histocompatibility complex class I on the muscle fibers causes an endoplasmic reticulum stress response, resulting in intracellular accumulation of misfolded glycoproteins and activation of the transcription factor NFκB, leading to further cytokine activation.
Molecular pathology and pathogenesis of inclusion‐body myositis
The basic hypothesis is that overexpression of AβPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade that leads to sporadic inclusion‐body myositis.
Inclusion-body myositis
Overall, the degenerative phenomena in s-IBM muscle fibers seem to be the major cause of the progressive, unstoppable weakness, rather than the lymphocytic inflammation.
Inclusion body myositis-like phenotype induced by transgenic overexpression of βAPP in skeletal muscle
Transgenic mice were derived in which selective overexpression of βAPP leads to the development of a subset of other histopathological and clinical features characteristic of IBM, including centric nuclei, inflammation, and deficiencies in motor performance, consistent with a pathogenic role for βAPP mismetabolism in human IBM.
Inflammatory, immune, and viral aspects of inclusion-body myositis
Muscle biopsies from patients with sporadic inclusion-body myositis (sIBM) consistently demonstrate that the inflammatory T cells almost invariably invade intact (not vacuolated) fibers, whereas the
Myostatin is increased and complexes with amyloid-β within sporadic inclusion-body myositis muscle fibers
It is suggested that myostatin/myostatin precursor, either alone, or bound to Aβ, may play a novel role in the pathogenesis of s-IBM.