Inclusion-Body Myositis: Newest Concepts of Pathogenesis and Relation to Aging and Alzheimer Disease

Abstract

We review the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic criteria of s-IBM. We discuss the possible pathogenic role of several themes, such as 1) increased amyloid-β precursor protein (AβPP) and of its fragment Aβ; 2) phosphorylation of tau protein; 3) oxidative stress; 4) abnormal a) signal-transduction, b) transcription, and c) RNA accumulation; 5) “junctionalization” and “myogenous” denervation; and 6) lymphocytic inflammation. Evidence is provided supporting our hypothesis that overexpression of AβPP within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease (AD) brain are discussed, and the possible cause and significance are addressed.