title: Inclusion-body myositis, a multifactorial muscle disease associated with aging: current concepts of pathogenesis.
abstract: OBJECTIVE
  Sporadic 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).
  
  
  RESULTS
  This review focuses on the current concepts of the pathogenesis of sporadic inclusion-body myositis. Both degeneration and mononuclear-cell inflammation are components of the pathology, but how each relates to the pathogenesis remains unclear. We suggest that an intramuscle fiber degenerative component is primary, leading to muscle-fiber destruction, while the lymphocytic inflammatory component may only slightly contribute to sporadic inclusion-body myositis muscle-fiber damage. Intracellular accumulation of amyloid-beta precursor protein, amyloid-beta, and amyloid-beta oligomers in an aging muscle-fiber cellular milieu, and other abnormalities, appear to be key pathogenic factors. We summarize intracellular molecular events and their consequences, and correlate findings in sporadic inclusion-body myositis muscle biopsies with inclusion-body myositis experimental models in tissue culture and in transgenic mice.
  
  
  CONCLUSIONS
  Treatment of sporadic inclusion-body myositis remains a challenge. Antiinflammatory approaches used so far are without major or enduring benefit. Possible new treatment avenues are suggested.
authors.affiliation: USC Neuromuscular Center, Department of Neurology, University of Southern California Keck School of Medicine, Good Samaritan Hospital, Los Angeles, California 90017-1912, USA. askanas@usc.edu
authors.forename: Valerie
authors.initials: V
authors.lastname: Askanas
authors.forename: W King
authors.initials: WK
authors.lastname: Engel
mesh_terms: D000375:Aging; D006801:Humans; D018979:Myositis, Inclusion Body / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*