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TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia
  1. C C Weihl1,
  2. P Temiz2,
  3. S E Miller1,
  4. G Watts3,
  5. C Smith4,
  6. M Forman5,
  7. P I Hanson6,
  8. V Kimonis7,
  9. A Pestronk1
  1. 1
    Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
  2. 2
    Celal Bayar University School of Medicine, Department of Pathology, Manisa, Turkey
  3. 3
    Department of Genetics, Boston Children’s Hospital, Boston, Massachusetts, USA
  4. 4
    University of Kentucky College of Medicine, Department of Neurology, Kentucky, USA
  5. 5
    Merck Research Laboratories, Boston, Massachusetts, USA
  6. 6
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri, USA
  7. 7
    Department of Genetics, University of California-Irvine, Irvine, California, USA
  1. Dr C C Weihl, Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA; weihlc{at}


TAR DNA binding protein-43 (TDP-43) is found in ubiquitinated inclusions (UBIs) in some frontotemporal dementias (FTD-U). One form of FTD-U, due to mutations in the valosin containing protein (VCP) gene, occurs with an inclusion body myopathy (IBMPFD). Since IBMPFD brain has TDP-43 in UBIs, we looked for TDP-43 inclusions in IBMPFD muscle. In normal muscle, TDP-43 is present in nuclei. In IBMPFD muscle, TDP-43 is additionally present as large inclusions within UBIs in muscle cytoplasm. TDP-43 inclusions were also found in 78% of sporadic inclusion body myositis (sIBM) muscles. In IBMPFD and sIBM muscle, TDP-43 migrated with an additional band on immunoblot similar to that reported in FTD-U brains. This study adds sIBM and hereditary inclusion body myopathies to the growing list of TDP-43 positive inclusion diseases.

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  • Competing interests: None.

  • Ethics approval: Obtained.

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