DNA single-strand breaks are increased in muscle diseases with rimmed vacuoles

Some pathological similarities between Alzheimer's disease and muscle disea ses with rimmed vacuoles (RV) have been pointed out. For example, several p athological hallmark proteins have been reported to be immunopositive in th e lesions of both diseases. Since apoptotic processes or primary DNA damage are suggested to play a role in the pathomechanism of Alzheimer's disease, we examined DNA double-strand breaks (DSB) and single-strand breaks (SSB) in the muscle biopsy specimens of several diseases, including muscle diseas es with RV. Although no DSB-positive myonuclei were detected in any muscles examined, the number of SSB-positive myonuclei markedly increased in the m uscles from cases with polymyositis and muscle diseases with RV. In polymyo sitis, SSB-positive myonuclei were observed in regenerating fibers and musc le fibers in the vicinity of inflammatory infiltrates, suggesting that the increase of SSB is due to muscle fiber regeneration following necrosis and inflammation. In muscle diseases with RV, however, SSB-positive myonuclei w ere observed in small angulated fibers and in morphologically normal fibers , regardless of necrosis, regeneration or inflammation. These findings sugg est that muscle diseases with RV may share a common pathological process in volving DNA damage.