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Nature of “Tau” immunoreactivity in normal myonuclei and inclusion body myositis

Authors

  • Mohammad Salajegheh MD,

    Corresponding author
    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
    2. Children's Hospital Informatics Program, Boston, Massachusetts
    • Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
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  • Jack L. Pinkus PhD,

    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
    2. Children's Hospital Informatics Program, Boston, Massachusetts
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  • Remedios Nazareno BS,

    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
    2. Children's Hospital Informatics Program, Boston, Massachusetts
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  • Anthony A. Amato MD,

    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
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  • Kenneth C. Parker PhD,

    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
    2. Children's Hospital Informatics Program, Boston, Massachusetts
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  • Steven A. Greenberg MD

    Corresponding author
    1. Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
    2. Children's Hospital Informatics Program, Boston, Massachusetts
    • Department of Neurology, Division of Neuromuscular Disease, Brigham and Women's Hospital, 75 Francis Street, and Harvard Medical School, Boston, Massachusetts 02115, USA
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Abstract

Sarcoplasmic accumulation of phosphorylated-tau has been widely stated to occur in and contribute to the pathogenesis of muscle disease in inclusion body myositis. Twenty inflammatory myopathy and 10 normal muscle samples along with a range of other tissues were stained with anti-“tau” antibodies (tau-5, pS422, and SMI-31). Myonuclear and sarcoplasmic fractions were prepared using differential solubilization and laser-capture microdissection, and immunoblots were performed using pS422 and SMI-31 antibodies. All three antibodies demonstrated anti-tau immunoreactivity in myonuclei from normal and diseased muscle, but not in nuclei from other tissues. Western blots showed pS422 and SMI-31 immunoreactivity against nuclear proteins outside the region expected for phosphorylated-tau. Antibodies previously reported to indicate abnormal accumulation of phosphorylated-tau in IBM myofibers react to normal myonuclei and recognize proteins other than tau. Normal myonuclei contain neurofilament H or other unidentified 200 kDa proteins with similar phosphorylated motifs accounting for SMI-31 immunoreactivity. Muscle Nerve, 2009

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