TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia
- C C Weihl1,
- P Temiz2,
- S E Miller1,
- G Watts3,
- C Smith4,
- M Forman5,
- P I Hanson6,
- V Kimonis7,
- A Pestronk1
- 1Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA
- 2Celal Bayar University School of Medicine, Department of Pathology, Manisa, Turkey
- 3Department of Genetics, Boston Children’s Hospital, Boston, Massachusetts, USA
- 4University of Kentucky College of Medicine, Department of Neurology, Kentucky, USA
- 5Merck Research Laboratories, Boston, Massachusetts, USA
- 6Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri, USA
- 7Department of Genetics, University of California-Irvine, Irvine, California, USA
- Dr C C Weihl, Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA;
- Received 23 August 2007
- Revised 21 November 2007
- Accepted 6 December 2007
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.
Competing interests: None.
Ethics approval: Obtained.