Chloroquine myopathy suggests that tau is degraded in lysosomes: implication for the formation of paired helical filaments in Alzheimer's disease.
We have found that amorphous tau deposits in chloroquine myopathy (CM), a vacuolar myopathy induced by the administration of chloroquine, a well-known lysosomotropic agent. The dynamics of tau in CM and immunocytochemistry strongly suggest that the accumulation of tau is due to defective tau degradation in the lysosomal compartment in the muscle. This observation may offer a new view on the formation of paired helical filaments in Alzheimer's disease: this selective protein degradation pathway may be defective and result in intracellular accumulation of tau, thereby forming the unusual filaments.
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Japan.
F
F
Oyama
N
N
Murakami
Y
Y
Ihara
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D000962:Antimalarials / Q000633:toxicity; D001921:Brain / Q000378:metabolism; D002738:Chloroquine / Q000633:toxicity; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism*; D018979:Myositis, Inclusion Body / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D000962:Antimalarials; D016875:tau Proteins; D002738:Chloroquine