Indeed, we recently showed that the overexpression of APP and PSEN1 with multiple FAD mutations were enough to induce robust Aβ deposition (amyloid plaques), and detergent-resistant, fibrillary p-tau aggregates in human neural cells cultured in our unique Matrigel-based three-dimensional (3D) culture system (Fig. 1), which has not been feasible in AD transgenic mouse models [17, 18, 31, 32]. This evidence concerns the gene PSEN1 and Alzheimer disease.