Inclusion Body Myositis

Polymyositis and Dermatomyositis Syndromes Polymyositis and Dermatomyositis Associated with Malignancy Inclusion Body Myositis (IBM)... 

Paulson, H. (2006) RNA interference as potential therapy for neurodegenerative disease applications to inclusion-body myositis Neurology, 66(2 suppl. 1), S114-S117. 

Askanas V, Engel WK (1998) Sporadic inclusion-body myositis and its similarities to Alzheimer disease brain. Recent approaches to diagnosis and pathogenesis, and relation to aging. Scand J Rheumatol 27 389-405... 

Maurage CA, Bussiere T, Sergeant N, Ghesteem A, Figarella-Bianger D, Ruchoux MM et al (2004) Tau aggregates are abnormally phosphorylated in inclusion body myositis and have... 

Alzheimer s disease inclusion-body myositis Amyloid fi peptide 40 and 42 Local... 

AP Amyloid-beta is a peptide of 39 3 amino acids that is the main constituent of amyloid plaques in the brains of Alzheimer s disease patients. Similar plaques appear in some variants of Lewy body dementia and in inclusion body myositis, a muscle disease. Ap also forms aggregates coating cerebral blood vessels in cerebral amyloid angiopathy. 

ILD occurs in approximately 40% of cases with a wide reported range of 5% to 65% (26,227-229,231-235). In a recent prospective study, of newly diagnosed PM/DM, pulmonary symptoms were present in 71% of patients and objective evidence of OLD (as judged by chest radiography, HRCT, or a restrictive ventilatory defect) was found in 65%, with 18% clinically silent (231). Adult patients with PM and DM are equally predisposed to develop ILD, but ELD is very frequent in Asian patients with CADM (26). ILD is extremely rare in inclusion-body myositis. 

PM/DM is an idiopathic inflammatory myopathy however, a number of autoantibody subclassifications correlate with features of clinical disease. When clinical muscle weakness is encountered in the pulmonary clinic, one recent addition to the laboratory armamentarium is the myositis antibody panel. These panels of autoantibody tests can define antibodies to many of the aminoacyl-tRNA synthetases and sometimes help define a CTD when previously not suspected. The most common syndrome is now termed the antisynthetase syndrome when autoantibodies are present in the setting of variable components of fever, myositis, Reynaud s phenomenon, arthritis, mechanic s hands, and ILD (40). Alternative PM/DM diagnostic strategies include targeting muscle weakness with magnetic resonance imaging (MRI) or electromyography (EMG) in preparation for muscle biopsy. It should be noted that some forms of idiopathic myopathy, such as inclusion body myositis, have not been associated with ILD but can present with respiratory impairment due to muscle weakness (41). 

Muscle Aging, Inclusion-Body Myositis and Myopathies, First Edition. Edited by Valerie Askanas and W. King Engel. 2012 Blackwell Publishing Ltd. Published 2012 hy Blackwell Publishing Ltd. 

Oldfors A, Moslem AR, Jonasson L et al. (2006) Mitochondrial abnormalities in inclusion-body myositis. Neurology 66, S49-55. 

Askanas V, Engel WK, Alvarez RB. (1993) Enhanced detection of congo-red-positive amyloid deposits in muscle fibers of inclusion body myositis and brain of... 

Engel WK, Askanas V. (1998) Treatment of inclusion-body myositis and hereditary inclusion-body myopathy with reference to pathogenic mechanisms personal experience. In Askanas V, Serratice G, Engel WK (eds). Inclusion-body Myositis and Myopathies. Cambridge University Press, Cambridge, pp. 351-382. 

Sporadic inclusion-body myositis (s-EBM) plus genetico-diabetoid-2 dysimmune peripheral neuropathy, the latter very treatable with IVIG (see below). 

Engel WK, AskanasV. (2006) Inclusion-body myositis clinical, diagnostic, and pathologic aspects. Neurology 66, S20-29. 

Oxidative damage to cells is a common phenomenon, and quality control of modified proteins is important to maintain normal cellular functions. In the cytoplasm, nucleus, and endoplasmic reticulum, the proteasome is involved in the removal of various types of proteins such as ubiquinated, misfolded, or unfolded proteins, and oxidized proteins. Abnormal inhibition of proteasome may contribute to neuro-degenerative diseases such as Alzheimer disease, Parkinson disease, Lewy body dementia, and Huntington disease [31-40]. Neuromuscular diseases, such as sporadic inclusion-body myositis (s-IBM) share several phenotypes described in the brain tissues of Alzheimer and Parkinson disease patients [41]. One such similarity to Alzheimer disease is the accumulation of amyloid-P (AP), phosphory-lated tau (p-tau), and ubiquitin, which are often found within these aggregates [42, 43]. In s-IBM patients, significant proteasome abnormalities were identified including, increased 26 S proteasome expression and abnormal accumulation of 26S proteasome, but reduced proteasome activities [44]. The inverse relationship between increased expression... 

Askanas V, Engel WK. (2008) Inclusion-body myositis muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer s and Parkinson s disease brains. Acta Neuropathol 116 (6), 583-595. 

Askanas V, Engel WK. (2003) Proposed pathogenetic cascade of inclusion-body myositis importance of amyloid-beta, misfolded proteins, predisposing genes, and aging. Curr Opin Rheumatol 15(6), 737-744. 

Askanas V, EngelWK. (2001) Inclusion-body myositis newest concepts of pathogenesis and relation to aging and Alzheimer disease. J Neuropathol Exp Neurol 60(1), 1-14. 

Fratta P, Engel WK, McFerrin J et al. (2005) Protea-some inhibition and aggresome formation in sporadic inclusion-body myositis and in amyloid-beta precursor protein-overexpressing cultured human muscle fibers. Am J Pathol 167(2), 517-526. 

Santorelli FM, SdaccoM, Tanji K et al. (1996) Multiple mitochondrial DNA deletions in sporadic inclusion body myositis a study of 56 patients. Ann Neurol 39 (6), 789-795. 

Pathogenesis of sporadic inclusion-body myositis role of aging and muscle-fiber degeneration, and accumulation of the same proteins as in Alzheimer and Parkinson brains... 

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