Immunohistochemical evidence for amyloid β in rat soleus muscle in chloroquine-induced myopathy

Deposition of amyloid β (Aβ) is one of the pathological hallmarks of brains affected with Alzheimer's disease (AD). The accumulation of Aβ have been observed in human myopathies with rimmed vacuoles (RVs) which might involve lysosomal function. Chloroquine, a potent lysosomotropic agent, induces muscle pathology in experimental animals similar to myopathy with RV. In this study, we demonstrate, for the first time, immunohistochemical evidence that Aβ and cathepsin D, a lysosomal enzyme, accumulate in vacuolated rat soleus muscle due to chloroquine-induced myopathy. These data indicate that lysosomes are important in the metabolism of amyloid precursor protein to generate Aβ. This experimental system seems to be useful not only to study basic mechanisms underlying RV myopathy but also to understand processing of amyloid precursor protein to Aβ in AD.