MAPT and Alzheimer disease: Studies in AD mouse models have shown that the barrier functions of the AIS—that control the traffic of tau and help restrict various isoforms of tau to specific neuronal domains—are disrupted in AD mouse models in the presence of phosphorylated tau and disorganized microtubules, or by the down-expression of AIS proteins like AnkyrinG or EB1, resulting in the missorting of hyperphosphorylated tau, which accumulates in the somatodendritic domain24–26.