Amyloid-beta deposition in skeletal muscle of transgenic mice - Possible model of inclusion body myopathy

Inclusion body myopathy is a progressive muscle disorder characterized by n uclear and cytoplasmic inclusions anc; vacuolation of muscle fibers. Affect ed muscle fibers contain deposits of congophilic amyloid, amyloid-beta immu noreactive filaments, and paired helical filaments, all of which are pathol ogical hallmarks of Alzheimer's disease in brain. Accumulations of amyloid- beta and its precursor are thought to play important roles in the pathogene sis of both inclusion body myopathy and Alzheimer's disease. Overexpression of mutant forms of beta protein precursor in transgenic mice by neuron-spe cific promoters has been reported to cause amyloid deposits in the brain. H ere we report that overexpression in transgenic mice of the signal plus 99- amino acid carboxyl-terminal sequences of beta protein precursor, under the control of a cytomegalovirus enhancer/beta-actin promoter, resulted in vac uolation and increasing accumulation of the 4-kd amyloid-beta and the carbo xyl-terminus in skeletal muscle fibers during aging. These deposits in tran sgenic muscle only rarely showed Congo red birefringence. Thus, overexpress ion of part of beta protein precursor in transgenic mice led to development of some of the characteristic features of inclusion body myopathy. These m ice may be a useful model of inclusion body myopathy, which shares a number of pathological markers with Alzheimer's disease.