APP and early-onset autosomal dominant Alzheimer disease: The intracellular domain of APP contains a number of phosphorylation sites (Tyr653 [20], Thr654 [8], Ser655 [21,22], Thr668 [23,24,25,26,27], Ser675 [28], Tyr682 [29,30], Thr686 [20] and Tyr687 [31]), which are all phosphorylated to various degrees in the brain of patients with Alzheimer’s disease in contrast to healthy brains, suggesting that the phosphorylation events may have a significant impact on the physiological function of APP.