TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia
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Date
2008
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Abstract
TAR DNA binding protein-43 (TDP-43) is found in ubiquitinated inclusions (UBIs) in some frontotemporal dementias (FTD-U). One form of FTD-LJ, 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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Keywords
Adenosine Triphosphatases , Antigens, CD8 , Cell Cycle Proteins , Dementia , Diagnosis, Differential , DNA-Binding Proteins , Electromyography , Humans , Muscle, Skeletal , Mutation, Missense , Myositis, Inclusion Body , Phosphorylation , Point Mutation , DNA binding protein , TDP 43 , unclassified drug , article , brain , cytoplasm , frontotemporal dementia , human , human cell , human tissue , immunoblotting , inclusion body myopathy , inclusion body myositis , muscle , muscle cell , myopathy , pathogenesis , priority journal