title: TDP-43 accumulation in inclusion body myopathy muscle suggests a common pathogenic mechanism with frontotemporal dementia.
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.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St Louis, Missouri 63110, USA. weihlc@neuro.wustl.edu
authors.forename: C C
authors.initials: CC
authors.lastname: Weihl
authors.forename: P
authors.initials: P
authors.lastname: Temiz
authors.forename: S E
authors.initials: SE
authors.lastname: Miller
authors.forename: G
authors.initials: G
authors.lastname: Watts
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Forman
authors.forename: P I
authors.initials: PI
authors.lastname: Hanson
authors.forename: V
authors.initials: V
authors.lastname: Kimonis
authors.forename: A
authors.initials: A
authors.lastname: Pestronk
mesh_terms: 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
chemical_list: 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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