IRS1 and Alzheimer disease: In summary, the present study unravels a novel mechanism of BPA-mediated pathological protein expression that involves the engagement of ERs, the disturbance of IR, IRS-1 and AKT signaling transduction and downstream GSK3α/β activation, and the increased expressions of APP, BACE-1, Aβ1–42, and p-tau, which ultimately culminate into an AD-like disease, as summarized in Fig. 8.