IRS1 and Alzheimer disease: To date, AD biomarkers derived from neuronal origin-enriched EVs include not only the main pathogenic proteins (p-tau and Aβ42) but also intracellular signaling molecules, such as phosphorylated IRS-1, Cathepsin-D, REST, LRP6, and others (Fiandaca et al., 2015; Goetzl et al., 2015a,b; Kapogiannis et al., 2015).