TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia.
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.
Weihl
C C
CC
Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA. weihlc@neuro.wustl.edu
Temiz
P
P
Miller
S E
SE
Watts
G
G
Smith
C
C
Forman
M
M
Hanson
P I
PI
Kimonis
V
V
Pestronk
A
A
D000251:Adenosine Triphosphatases / Q000235:genetics; D016827:CD8 Antigens / Q000276:immunology; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000276:immunology*; D003704:Dementia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D004576:Electromyography; D006801:Humans; D018482:Muscle, Skeletal / Q000276:immunology / Q000294:innervation / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics; D018979:Myositis, Inclusion Body / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D000074405:Valosin Containing Protein
D016827:CD8 Antigens; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
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