BETA-AMYLOID PRECURSOR PROTEIN MESSENGER-RNA IS INCREASED IN INCLUSION-BODY MYOSITIS MUSCLE

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