APOE and Alzheimer disease: The finding that Aβ deposition is specifically elevated in apoE4-positive AD patients [25], combined with in vivo and in vitro model studies, which revealed that apoE4 and the amyloid cascade interact synergistically [12,32-36], led to the suggestion that the pathological effects of apoE4 are mediated via cross-talk with the amyloid cascade [37-40].