title: New advances in the understanding of sporadic inclusion-body myositis and hereditary inclusion-body myopathies.
abstract: This review emphasizes new advances in seeking the pathogenic mechanisms of sporadic inclusion-body myositis and hereditary inclusion-body myopathy syndromes. Clinical and pathologic similarities and differences between sporadic and hereditary forms are described. Hypotheses are presented regarding the possible causes and consequences of abnormally accumulated intramyofiber beta-amyloid precursor protein (beta APP) (including beta-amyloid protein and C- and N-terminal epitopes), hyperphosphorylated tau, alpha 1-antichymotrypsin, apolipoprotein E, prion protein, ubiquitin, nicotinic acetylcholine receptor and its 43-kD associated protein, fibroblast growth factor, and transforming growth factor-beta. Also increased are beta APP mRNA and prion protein mRNA. Striking similarities between the pathology of muscle specimens from sporadic inclusion-body myositis and samples from the brains of patients with Alzheimer's disease in regard to Congo red positivity and accumulations of several proteins are discussed. Because most of the proteins that pathologically accumulate throughout the abnormal muscle fibers also accumulate focally at normal human neuromuscular junctions, the possible "junctionalization" of nonjunctional nuclei as a pathogenic mechanism in the muscle fiber is discussed.
authors.affiliation: Neuromuscular Center, University of Southern California School of Medicine, Hospital of the Good Samaritan, Los Angeles 90017-1912, USA.
authors.forename: V
authors.initials: V
authors.lastname: Askanas
authors.forename: W K
authors.initials: WK
authors.lastname: Engel
mesh_terms: D003937:Diagnosis, Differential; D006801:Humans; D018979:Myositis, Inclusion Body / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology