Molecular pathology and pathogenesis of inclusion‐body myositis

Abstract

We summarize the molecular phenotype, diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion‐body myositis (s‐IBM), a muscle disease usually of persons over age 50. On the basis of our research, several processes seem to be important in relation to the still‐speculative pathogenesis: 1) increased transcription and accumulation of amyloid‐β precursor protein (AβPP), and accumulation of its proteolytic fragment Aβ; 2) abnormal accumulation of cholesterol, caveolin‐1, and apolipoprotein E; 3) oxidative stress; 4) accumulations of intramuscle fiber multiprotein aggregates; and 5) evidence that unfolded/misfolded proteins participate in s‐IBM pathogenesis. Our basic hypothesis is that overexpression of AβPP within the aging muscle fibers is an early upstream event causing a subsequent pathogenic cascade. Microsc. Res. Tech. 67:114–120, 2005.