TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia

CC Weihl, P Temiz, SE Miller, G Watts… - Journal of Neurology …, 2008 - jnnp.bmj.com
CC Weihl, P Temiz, SE Miller, G Watts, C Smith, M Forman, PI Hanson, V Kimonis
Journal of Neurology, Neurosurgery & Psychiatry, 2008jnnp.bmj.com
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 …
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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