This report summarizes clinical features and diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis. On the basis of the authors' research, several processes seem to be important in relation to the still-speculative pathogenesis: increased transcription and accumulation of amyloid-b precursor protein and accumulation of its proteolytic fragment amyloid-b; abnormal accumulation of components related to lipid metabolism (eg, low-density lipoprotein receptors and cholesterol; accumulation of cholesterol is possibly caused by its abnormal trafficking); oxidative stress; accumulations of other Alzheimer-related proteins including phosphorylated tau; a milieu of muscle cellular aging in which these changes occur. The authors' basic hypothesis is that overexpression of amyloid-b precursor protein within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between inclusion-body myositis muscle and Alzheimer's disease brain are discussed.