title: Co-localization of amyloid-associated proteins with amyloid beta in rat soleus muscle in chloroquine-induced myopathy: a possible model for amyloid beta formation in Alzheimer's disease.
abstract: Chloroquine, a potent lysosomotropic agent, induces myopathy in experimental animals similar to rimmed vacuole (RV) myopathy in humans. The abnormal accumulation of amyloid beta protein (A beta), 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 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-antichymotrypsin, apolipoprotein E, SP-40,40 and ubiquitin co-localize with A beta 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 beta, and the role of amyloid-associated proteins in terms of the pathogenesis of AD.
authors.affiliation: Department of Microbiology, Sapporo Medical University, School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuzuki
authors.forename: R
authors.initials: R
authors.lastname: Fukatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Takamaru
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: N
authors.initials: N
authors.lastname: Mafune
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Fujii
authors.forename: N
authors.initials: N
authors.lastname: Takahata
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002738:Chloroquine / Q000494:pharmacology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D002738:Chloroquine