Acta Neuropathologica

, Volume 120, Issue 5, pp 661–666 | Cite as

Novel demonstration of amyloid-β oligomers in sporadic inclusion-body myositis muscle fibers

  • Anna Nogalska
  • Carla D’Agostino
  • W. King Engel
  • William L. Klein
  • Valerie Askanas
Original Paper


Accumulation of amyloid-β (Aβ) within muscle fibers has been considered an upstream step in the development of the s-IBM pathologic phenotype. Aβ42, which is considered more cytotoxic than Aβ40 and has a higher propensity to oligomerize, is preferentially increased in s-IBM muscle fibers. In Alzheimer disease (AD), low-molecular weight Aβ oligomers and toxic oligomers, also referred to as “Aβ-Derived Diffusible Ligands” (ADDLs), are considered strongly cytotoxic and proposed to play an important pathogenic role. ADDLs have been shown to be increased in AD brain. We now report for the first time that in s-IBM muscle biopsies Aβ-dimer, -trimer, and -tetramer are identifiable by immunoblots. While all the s-IBM samples we studied had Aβ-oligomers, their molecular weights and intensity varied between the patient samples. None of the control muscle biopsies had Aβ oligomers. Dot-immunoblots using highly specific anti-ADDL monoclonal antibodies also showed highly increased ADDLs in all s-IBM biopsies studied, while controls were negative. By immunofluorescence, in some of the abnormal s-IBM muscle fibers ADDLs were accumulated in the form of plaque-like inclusions, and were often increased diffusely in very small fibers. Normal and disease-controls were negative. By gold-immuno-electron microscopy, ADDL-immunoreactivities were in close proximity to 6–10 nm amyloid-like fibrils, and also were immunodecorating amorphous and floccular material. In cultured human muscle fibers, we found that inhibition of autophagy led to the accumulation of Aβ oligomers. This novel demonstration of Aβ42 oligomers in s-IBM muscle biopsy provides additional evidence that intra-muscle fiber accumulation of Aβ42 oligomers in s-IBM may contribute importantly to s-IBM pathogenic cascade.


Sporadic inclusion-body myositis (s-IBM) Amyloid-β oligomers Amyloid-β derived diffusible ligands (ADDLs) Amyloid-β42 Amyloid β precursor protein (AβPP) Lysosomal inhibition Autophagy 



This study was supported by grants (to VA) from the National Institutes of Health (AG 16768 Merit Award), the Muscular Dystrophy Association, and the Helen Lewis Research Fund. Maggie Baburyan provided excellent technical assistance in electron microscopy.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Anna Nogalska
    • 1
  • Carla D’Agostino
    • 1
  • W. King Engel
    • 1
  • William L. Klein
    • 2
  • Valerie Askanas
    • 1
  1. 1.Department of Neurology, USC Neuromuscular Center, Good Samaritan HospitalUniversity of Southern California Keck School of MedicineLos AngelesUSA
  2. 2.Department of Neurology and PhysiologyNorthwestern UniversityEvanstonUSA

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