INS and Alzheimer disease: Despite that, prolonged IR stimulation is known to result in IRS-1 inhibition through negative feedback mechanisms [105], though the early alteration of O-GlcNAcylation cycling may interfere with correct insulin signaling in young Ts2 mice, as observed in AD mice [55], paving the way for the onset of insulin resistance condition observed in DS brain [16, 22, 77].