APP and Alzheimer disease: Previous studies reported that Grb2 expression is upregulated in the brains of AD patients and model mice and suggested that Grb2 contributes to brain insulin resistance and AD pathogenesis through interactions with APP and NADPH oxidase 4 (Nox4) (Bruce-Keller et al., 2011; Wu and Williams, 2012; Roy et al., 2014; Majumder et al., 2017, 2021; Park et al., 2021).