Abstract:Alzheimer’s disease (AD), as a progressive neurodegenerative disease with complex pathogenesis and no effective cure, has become a major challenge for global public health. Recent studies have revealed that insulin resistance (IR) may be one of the important pathological mechanisms of AD. This artice focuses on the pivotal position of brain insulin resistance (BIR) between metabolic disorders and AD pathology, systematically elucidate the multidimensional regulatory effects of insulin and insulin signaling on neuronal energy utilization, synaptic plasticity, and neuroglial cell populations in the brain, and investigate in detail the pathological associations between BIR and the core pathological features of AD, such as β-amyloid, and Tau protein pathology. Meanwhile,this review summarizes the latest progress of BIR assessment methods and model construction, aiming to provide theoretical support and research direction for the early diagnosis and intervention strategy of AD based on insulin signaling.