DIFFERENCE IN EXPRESSION OF PHOSPHORYLATED TAU-EPITOPE BETWEEN SPORADIC INCLUSION-BODY MYOSITIS AND HEREDITARY INCLUSION-BODY MYOPATHIES

Sporadic inclusion-body myositis (s-IBM) and the hereditary inclusion- body myopathies (h-IBMs) are severe and progressive muscle diseases, c haracterized pathologically by vacuolated muscle fibers containing pai red-helical filaments (PHFs). An interesting feature of the s- and h-I BM muscle phenotype is its striking similarity to Alzheimer-disease (A D) brain. We immunostained muscle biopsies of 9 s-IBM patients, 9 auto somal-recessive h-IBM patients, 1 autosomal-dominant h-IBM patient, an d 18 normal and disease-controls with several antibodies known to reac t 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 vacuolate d muscle fibers had strongly immunoreactive inclusions with SMI-31, an d by immuno-electronmicroscopy SMI-31 was exclusively localized to PHF s. Approximately 40 to 50% of both s- and h-IBM vacuolated muscle fibe rs were also immunoreactive with AT8 antibody. To the contrary, in h-I BM, there was no immunoreactivity with SMI-310 and PHF-1 antibodies, w hereas in s-IBM the vacuolated muscle fibers had strong immunoreactivi ty with those two antibodies. By immunoelectronmicroscopy, SMI-310 and PHF-1 also were localized to PHFs. Within s-IBM muscle fibers, the st ructures immunoreactive with SMI-310 were congophilic, whereas h-IBM m uscle fibers did not have congophilia. Our studies: (a) demonstrate a distinct difference between s-IBM and the h-IBMs in regard to the expr ession of immunoreactive phosphorylated tau and congophilia; (b) demon strate a new ''diagnostic duo'' combination of SMI-31 and SMI-310 anti bodies 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 m echanisms may be active in both diseases.