Twisted tubulofilaments of inclusion body myositis muscle resemble paired helical filaments of Alzheimer brain and contain hyperphosphorylated tau

• Published in: The American journal of pathology Vol. 144; no. 1; pp. 177 - 187
• Main Authors: Askanas, V, Engel, WK, Bilak, M, Alvarez, RB, Selkoe, DJ
• Format: Journal Article
• Language: English
• Published: United States ASIP 01.01.1994
• Subjects: Adult; Aged; Alzheimer Disease - pathology; Brain - ultrastructure; Humans; Immunohistochemistry; Inclusion Bodies - ultrastructure; Microscopy, Fluorescence; Microscopy, Immunoelectron; Middle Aged; Muscles - ultrastructure; Myositis - genetics; Myositis - pathology; Phosphorylation; tau Proteins - metabolism
• ISSN: 0002-9440; 1525-2191

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 and disease controls. We used the following well-characterized antibodies against tau protein: Tau-1, Alz-50, and anti-paired helical filament (PHF) antiserum. By light microscopy, in all S-IBM muscle biopsies virtually all vacuoles immunoreactive for ubiquitin and beta-amyloid protein also contained inclusions immunoreactive with Alz-50 and anti-PHF antiserum. With tau-1 antibody, strong immunoreactivity in the vacuoles was obtained only after dephosphorylation of muscle sections. By electronmicroscopy, all three antibodies immunodecorated exclusively cytoplasmic 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 fibers were the inclusions immunoreactive with Alz-50. In six H-IBM patients there were no tau-1 immunoreactive inclusions in any of their vacuolated muscle fibers; in one patient, 24% of the vacuolated fibers had tau-1 immunoreactivity. By demonstrating that hyperphosphorylated tau, which is characteristic of Alzheimer brain PHFs, is a component of S-IBM-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 Alzheimer brain and S-IBM muscle may share some similar mechanisms. Whether the difference in tau immunoreactivity between S-IBM and most of the H-IBM patients reflects a difference in genetically determined transcriptional or posttranslational modifications of tau protein or other factors remains to be determined.