Activation of the γ-secretase complex and presence of γ-secretase-activating protein may contribute to Aβ42 production in sporadic inclusion-body myositis muscle fibers

► γ-secretase components, presenilin1, Pen2, and nicastrin, are increased in s-IBM muscle. ► γ-secretase activity is increased in s-IBM muscle fibers. ► A novel γ-secretase activating protein (GSAP) is present in s-IBM muscle fibers. ► In cultured human muscle, autophagy inhibition increases γ-secretase activity. ► Experimentally inhibited autophagy leads to increase of Aβ42.