title: Newest pathogenetic considerations in inclusion-body myositis: possible role of amyloid-beta, cholesterol, relation to aging and to Alzheimer's disease.
abstract: This report summarizes clinical features and diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis. On the basis of the authors' research, several processes seem to be important in relation to the still-speculative pathogenesis: increased transcription and accumulation of amyloid-b precursor protein and accumulation of its proteolytic fragment amyloid-b; abnormal accumulation of components related to lipid metabolism (eg, low-density lipoprotein receptors and cholesterol; accumulation of cholesterol is possibly caused by its abnormal trafficking); oxidative stress; accumulations of other Alzheimer-related proteins including phosphorylated tau; a milieu of muscle cellular aging in which these changes occur. The authors' basic hypothesis is that overexpression of amyloid-b precursor protein within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between inclusion-body myositis muscle and Alzheimer's disease brain are discussed.
authors.affiliation: University of Southern California Neuromuscular Center, Good Samaritan Hospital, 637 South Lucas Avenue, Los Angeles, CA 90017-1912, USA. askanas@hsc.usc.edu
authors.forename: Valerie
authors.initials: V
authors.lastname: Askanas
authors.forename: W King
authors.initials: WK
authors.lastname: Engel
mesh_terms: D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000150:complications; D009132:Muscles / Q000473:pathology; D009154:Mutation; D018979:Myositis, Inclusion Body / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D011228:Prealbumin / Q000235:genetics; D018110:Receptors, Lipoprotein / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D011228:Prealbumin; D018110:Receptors, Lipoprotein