APP and Alzheimer disease: The origin of BBB dysfunction during AD is not known, but APP expression leading to the generation of abeta may be directly involved in this process as BBB leakiness has been demonstrated in a number of AD transgenic animals models in which forms of APP are overexpressed, including the Tg2576 that overexpresses the human APP695 containing the double missense Swedish mutations (K670N/M671L) that causes a form of early-onset AD [22], [24], [25], [26].