ABNORMAL ACCUMULATION OF PRION PROTEIN MESSENGER-RNA IN MUSCLE-FIBERSOF PATIENTS WITH SPORADIC INCLUSION-BODY MYOSITIS AND HEREDITARY INCLUSION-BODY MYOPATHY

Sporadic inclusion-body myositis is the most common Progressive muscle disease of older patients. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired heli cal filaments and 6 to 10-nm fibrils, both resembling those of Alzheim er brain, and Congo-red positivity. Hereditary inclusion-body myopathy designates patients cytopathologically similar but without inflammati on. In both muscle diseases, prion, and several proteins characteristi c of Alzheimer brain-eg, beta amyloid protein and hyperphosphorylated tau (which normally are expressed mainly in neurons), and apolipoprote in E-are abnormally accumulated in vacuolated muscle fibers, by unknow n mechanisms. We now demonstrate in both muscle diseases that prion mR NA is strongly expressed ill the vacuolated muscle fibers, which sugge sts that their accumulated prion protein results, at least partly, fro m increased gene expression This, to our knowledge, is the first demon stration of abnormally increased prion mRNA in human disease. Another novel finding is the increased prion mRNA in human muscle macrophages, and both increased prion protein and prion mRNA ill regenerating musc le fibers. The latter indicates that prion may play a role in human mu scle development.