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 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.
Askanas
V
V
Department of Neurology, University of Southern California School of Medicine, Los Angeles.
Engel
W K
WK
Bilak
M
M
Alvarez
R B
RB
Selkoe
D J
DJ
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000648:ultrastructure*; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure*; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009132:Muscles / Q000648:ultrastructure*; D009220:Myositis / Q000235:genetics / Q000473:pathology*; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins