title: Difference in expression of phosphorylated tau epitopes between sporadic inclusion-body myositis and hereditary inclusion-body myopathies.
abstract: Sporadic inclusion-body myositis (s-IBM) and the hereditary inclusion-body myopathies (h-IBMs) are severe and progressive muscle diseases, characterized pathologically by vacuolated muscle fibers containing paired-helical filaments (PHFs). An interesting feature of the s- and h-IBM muscle phenotype is its striking similarity to Alzheimer-disease (AD) brain. We immunostained muscle biopsies of 9 s-IBM patients, 9 autosomal-recessive h-IBM patients, 1 autosomal-dominant h-IBM patients, and 18 normal and disease-controls with several antibodies known to react with the hyperphosphorylated tau of AD-PHFs. Those included SMI-31, SMI-310, PHF-1, and AT8. In both s- and h-IBM, virtually all vacuolated muscle fibers had strongly immunoreactive inclusions with SMI-31, and by immuno-electronmicroscopy SMI-31 was exclusively localized to PHFs. Approximately 40 to 50% of both s- and h-IBM vacuolated muscle fibers were also immunoreactive with AT8 antibody. To the contrary, in h-IBM, there was no immunoreactivity with SMI-310 and PHF-1 antibodies, whereas in s-IBM the vacuolated muscle fibers had strong immunoreactivity with those two antibodies. By immunoelectronmicorscopy, SMI-310 and PHF-1 also were localized to PHFs. Within s-IBM muscle fibers, the structures immunoreactive with SMI-310 were congophilic, whereas h-IBM muscle fibers did not have congophilia. Our studies: (a) demonstrate a distinct difference between s-IBM and the h-IBMs in regard to expression of immunoreactive phosphorylated tau and congophilia; (b) demonstrate a new "diagnostic duo" combination of SMI-31 and SMI-310 antibodies for identifying and distinguishing s-IBM and the h-IBMs; and (c) provide another close similarity of pathologic phenotypes between s-IBM muscle and AD brain, suggesting that similar cellular pathogenic mechanisms may be active in both diseases.
authors.affiliation: USC Neuromuscular Center, University of Southern California School of Medicine, Good Samaritan Hospital, Los Angeles 90017-1912, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mirabella
authors.forename: R B
authors.initials: RB
authors.lastname: Alvarez
authors.forename: M
authors.initials: M
authors.lastname: Bilak
authors.forename: W K
authors.initials: WK
authors.lastname: Engel
authors.forename: V
authors.initials: V
authors.lastname: Askanas
mesh_terms: D000328:Adult; D000368:Aged; D003224:Congo Red; D000939:Epitopes; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000648:ultrastructure*; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D013194:Staining and Labeling; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D000939:Epitopes; D016875:tau Proteins; D003224:Congo Red