For both APPPS1 mice and human AD, stable amyloid deposits tend to emerge first in the entorhinal cortex and hippocampus, likely due to a failure in the transport of processed APP along axonal pathways from the entorhinal cortex,36, 59, 60, 61, 62 and in time, intense trafficking of soluble/insoluble amyloid over the IPAD pathway leads to the obliteration of these vessels, a hypothesis that aligns perfectly well with our result of decreased plaque–vessel association in the hippocampus after AQP4 facilitation. This evidence concerns the gene APP and Alzheimer disease.