INS and early-onset autosomal dominant Alzheimer disease: In this review, we discuss about insulin signaling in the brain and the role of insulin resistance in neurodegenerative diseases such as Alzheimer’s disease (AD) with a particular focus on the association of protein O-GlcNAcylation with impaired glucose utilization possibly due to insulin resistance and the role of O-GlcNAcylation on the pathology of AD.