Co-localization of amyloid-associated proteins with amyloid β in rat soleus muscle in chloroquine-induced myopathy: a possible model for amyloid β formation in Alzheimer's disease

Chloroquine, a potent lysosomotropic agent, induces myopathy in experimental animals similar to rimmed vacuole (RV) myopathy in humans. The abnormal accumulation of amyloid β protein (A β), which is the invariable pathological alterations in the brains affected by Alzheimer's disease (AD), has been demonstrated in denervated soleus muscle fibers in chloroquine-induced myopathy in rats. In AD affected brains, a variety of additional proteins are associated with the extracellular deposition of A β, which leads to the intracellular accumulation of neurofibrillary tangles and finally to neuronal death. In this study, we demonstrate that amyloid-associated proteins,α₁-antichymotrypsin, apolipoprotein E, SP-40,40 and ubiquitin co-localize with A β in vacuolated muscle fibers in chloroquine-induced myopathy. There are striking similarities in immunopathology between experimental RV myopathy and AD. Chloroquine-induced myopathy in rats provides a suitable model not only to obtain insight into the basic mechanisms underlying RV formation in muscle, but also to understand amyloid precursor protein processing into A β, and the role of amyloid-associated proteins in terms of the pathogenesis of AD.