βAPP gene transfer into cultured human muscle induces inclusion-body myositis aspects

Abstract

Direct transfer of the beta-amyloid precursor protein (beta APP) gene into cultured normal human muscle, using recombinant adenovirus vector, was sufficient to induce several of the typical light microscopic, electron microscopic (EM), and EM-immunochemical aspects of the inclusion-body myositis (IBM) phenotype, including congophilia, clusters of amyloid-beta-positive 6-10 nm filaments, and 15-21 nm tubulofilamentous inclusions in the nuclei. Our results suggest that excessive production of intracellular beta APP may play an important role in the pathogenic cascade leading to the IBM phenotype.