Immunohistochemical evidence for amyloid beta in rat soleus muscle in chloroquine-induced myopathy.
Deposition of amyloid beta (A beta) is one of the pathological hallmarks of brains affected with Alzheimer's disease (AD). The accumulation of A beta 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 A beta 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 A beta. 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 A beta in AD.
Tsuzuki
K
K
Department of Microbiology, Sapporo Medical University, School of Medicine, Japan.
Fukatsu
R
R
Takamaru
Y
Y
Kimura
K
K
Abe
M
M
Shima
K
K
Fujii
N
N
Takahata
N
N
D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009132:Muscles / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D002738:Chloroquine