TWISTED TUBULOFILAMENTS OF INCLUSION-BODY MYOSITIS MUSCLE RESEMBLE PAIRED HELICAL FILAMENTS OF ALZHEIMER BRAIN AND CONTAIN HYPERPHOSPHORYLATED-TAU

We immunostained muscle biopsies of 8 patients with sporadic inclusion body myositis (S-IBM), 7 patients with autosomal recessive hereditary inclusion body myopathy (H-IBM) (both diseases being characterized by similar muscle fiber vacuoles containing inclusions), and 11 normal a nd disease controls. We used the following well-characterized antibodi es against tau protein: Tau-1, Alz-50, and anti-paired belical filamen t (PHF) antiserum. By light microscopy, in all S-IBM muscle biopsies v irtually all vacuoles immunoreactive for ubiquitin and beta-amyloid pr otein also contained inclusions immunoreactive Alz-50 and anti-PHF ant iserum. With tau-1 antibody, strong immunoreactivity in the vacuoles w as obtained only after dephosphorylation of muscle sections. By electr onmicroscopy, all three antibodies immunodecorated exclusively cytopla smic twisted tubulofilaments (TTFs). In H-IBM, virtually all ubiquitin and beta-amyloid-positive muscle fiber vacuoles contained inclusions immunoreactive with anti-PHF antiserum, but in only 40% of those fiber s were the inclusions immunoreactive with Alz-50. In six H-IBM patient s there were no tau-1 immunoreactive inclusions in any of their vacuol ated muscle fibers; in one patient, 24% of the vacuolated fibers had t au-1 immunoreactivity. By demonstrating that hyperphosphorylated tau, which is characteristic of Alzheimer brain PHFs, is a component of S-I BM-muscle TTFs (which are also ultrastructurally similar to PHFs), our study: 1) provides the first demonstration of abnormally accumulated tau in nonneural tissue and 2) suggests that the cytopathogenesis in A lzheimer brain and S-IBM muscle may share some similar mechanisms. Whe ther the difference in tau immunoreactivity between S-IBM and most of the H-IBM patients reflects a difference in genetically determined tra nscriptional or posttranslational modifications of tau protein or othe r factors remains to be determined.