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Vacuolated muscle fibers in muscle biopsies of 8 out of 8 inclusion body myositis (IBM) patients, including 2 hereditary patients, manifested increased mRNA for the [beta]-amyloid precursor protein ([beta]APP) that contains Kunitz-type protease inhibitor motif. In affected fibers, increased [beta]APP-mRNA corresponded to abnormally accumulated [beta]APP immunoreactivity (including [beta]-amyloid protein epitope). In normal human muscle fibers increased [beta]APP-mRNA was present only at the neuromuscular junctions. Our study (a) suggests that abnormally accumulated [beta]APP in IBM vacuolated fibers results, at least partly, from increased [beta]APP generation, and (b) provides the first demonstration of up-regulated [beta]APP-mRNA in pathologic human tissue other than brain of Alzheimer's disease and Down's syndrome.

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