Given BACE1 elevation positioned at the intersection of a vicious cycle between Aβ accumulation and insulin resistance (Figure 1), BACE1 biomarkers are especially important under diabetic or prediabetic conditions and can be used in combination with other early AD biomarkers (Aisen et al., 2022; Rafii and Aisen, 2023) as well as sensitive cognitive measures (Ohno, 2023, 2024) to identify high-risk individuals who would benefit from preventive BACE1 inhibitor treatment. Here, BACE1 is linked to Insulin resistance.