TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia. Issue 10 (16th September 2008)

• Record Type: Journal Article
• Authors: Weihl, C C; Temiz, P; Miller, S E; Watts, G; Smith, C; Forman, M; Hanson, P I; Kimonis, V; Pestronk, A
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 79:Issue 10(2008)
• Page Start: 1186
• Page End: 1189
• Publication Date: 2008-09-16
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp.2007.131334
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.