Acta Neuropathologica

, Volume 117, Issue 5, pp 569–574

Amyloid-β42 is preferentially accumulated in muscle fibers of patients with sporadic inclusion-body myositis

  • Gaetano Vattemi
  • Anna Nogalska
  • W. King Engel
  • Carla D’Agostino
  • Frederic Checler
  • Valerie Askanas
Original Paper

DOI: 10.1007/s00401-009-0511-6

Cite this article as:
Vattemi, G., Nogalska, A., King Engel, W. et al. Acta Neuropathol (2009) 117: 569. doi:10.1007/s00401-009-0511-6

Abstract

Sporadic inclusion-body myositis (s-IBM) is the only muscle disease in which accumulation of amyloid-β (Aβ) in abnormal muscle fibers appears to play a key pathogenic role. Increased amyloid-β precursor protein (AβPP) and Aβ accumulation have been reported to be upstream steps in the development of the s-IBM pathologic phenotype, based on cellular and animal models. Aβ is released from AβPP as a 40 or 42 aminoacid peptide. Aβ42 is considered more cytotoxic than Aβ40, and it has a higher propensity to aggregate and form amyloid fibrils. Using highly specific antibodies, we evaluated in s-IBM muscle biopsies intra-muscle fiber accumulation of Aβ40 and Aβ42-immunoreactive aggregates by light- and electron-microscopic immunocytochemistry, and quantified their amounts by ELISA. In s-IBM, 80–90% of the vacuolated muscle fibers and 5–20% of the non-vacuolated muscle fibers contained plaque-like Aβ42-immunoreactive inclusions, while only 69% of those fibers also contained Aβ40 deposits. By immuno-electronmicroscopy, Aβ42 was associated with 6–10 nm amyloid-like fibrils, small electron-dense floccular clumps and larger masses of amorphous material. Aβ40 was present only on small patches of floccular clumps and amorphous material; it was not associated with 6–10 nm amyloid fibrils. By ELISA, in s-IBM muscle biopsies Aβ42 was present in values 8.53-44.7 pg/ml, while Aβ40 was not detectable; normal age-matched control biopsies did not have any detectable Aβ42 or Aβ40. Thus, in s-IBM muscle fibers, Aβ42 is accumulated more than Aβ40. We suggest that Aβ42 oligomers and their cytotoxicity may play an important role in the s-IBM pathogenesis.

Keywords

Inclusion-body myositisAmyloid-β42Amyloid-β40Amyloid-βAmyloid-β oligomersCytotoxicity

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Gaetano Vattemi
    • 1
  • Anna Nogalska
    • 1
  • W. King Engel
    • 1
  • Carla D’Agostino
    • 1
  • Frederic Checler
    • 2
  • Valerie Askanas
    • 1
  1. 1.USC Neuromuscular Center, Department of NeurologyUniversity of Southern California Keck School of Medicine, Good Samaritan HospitalLos AngelesUSA
  2. 2.IPMC and IN2M, UMR6097 CNRS/UNSAéquipe labellisée “Fondation pour la Recherche Médicale”ValbonneFrance