GO-LOCALIZATION OF AMYLOID-ASSOCIATED PROTEINS WITH AMYLOID-BETA IN RAT SOLEUS MUSCLE IN CHLOROQUINE-INDUCED MYOPATHY - A POSSIBLE MODEL FOR AMYLOID-BETA FORMATION IN ALZHEIMERS-DISEASE

Chloroquine, a potent lysosomotropic agent, induces myopathy in experi mental animals similar to rimmed vacuole (RV) myopathy in humans. The abnormal accumulation of amyloid beta protein (A beta), which is the i nvariable pathological alterations in the brains affected by Alzheimer 's disease (AD), has been demonstrated in denervated soleus muscle fib ers in chloroquine-induced myopathy in rats. In AD affected brains, a variety of additional proteins are associated with the extracellular d eposition of A beta, which leads to the intracellular accumulation of neurofibrillary tangles and finally to neuronal death. In this study, we demonstrate that amyloid-associated proteins, alpha(1)-antichymotry psin, apolipoprotein E, SP-40,40 and ubiquitin co-localize with A beta in vacuolated muscle fibers in chloroquine-induced myopathy. There ar e striking similarities in immunopathology between experimental RV myo pathy 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 prot ein processing into A beta, and the role of amyloid-associated protein s in terms of the pathogenesis of AD.