title: Sporadic inclusion-body myositis and its similarities to Alzheimer disease brain. Recent approaches to diagnosis and pathogenesis, and relation to aging.
abstract: Sporadic inclusion-body myositis (s-IBM) is the most common, debilitating and progressive muscle disease beginning at the age 50 or later. The most characteristic pathologic feature is vacuolar degeneration of muscle fibers accompanied by intrafiber congophilia and clusters ("tangles") of paired-helical filaments, containing phosphorylated tau. An unusual feature of sporadic inclusion-body myositis is accumulation within its abnormal muscle fibers of several proteins that are characteristic of Alzheimer disease brain, including epitopes of beta-amyloid precursor protein (betaAPP), phosphorylated tau, alpha-1-antichymotrypsin, apolipoprotein E, and presenilin-1. Indicators of oxidative stress are also present within abnormal s-IBM muscle fibers. In this review, we describe new advances seeking the pathogenic mechanism of sporadic inclusion-body myositis. We hypothesize on the possible pathogenic role of abnormally accumulated proteins, and we propose that important contributory factors leading to inclusion-body myositis are the milieu of muscle-fiber aging and oxidative stress. In addition, we present evidence that overexpression of adenovirus-transferred betaAPP gene in cultured human muscle fibers induces aspects of the inclusion-body myositis phenotype, and suggest that betaAPP-overexpression is an early event in the pathogenic cascade causing inclusion-body myositis.
authors.forename: V
authors.initials: V
authors.lastname: Askanas
authors.forename: W K
authors.initials: WK
authors.lastname: Engel
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D001327:Autoimmune Diseases / Q000150:complications; D015490:HTLV-I Infections / Q000150:complications / Q000453:epidemiology; D006801:Humans; D007249:Inflammation / Q000150:complications; D009132:Muscles / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000821:virology; D016262:Postpoliomyelitis Syndrome / Q000150:complications; D011228:Prealbumin / Q000235:genetics; D016036:Seroepidemiologic Studies
chemical_list: D011228:Prealbumin