Here, we have developed a human 3D neural culture model using iPSC-derived NSC from healthy individuals and FAD patients with PSEN1 mutations-L286V, M146L or A246E, maintained for 12 weeks post-3D plating in vitro. Our model shows early signs of neuronal maturation in the 3D cultures, increased total Tau in 3D-AD when compared to the 3D controls, and early signs of Tau insolubility from cells derived from iPSCs from patients with PSEN1 mutations. Here, PSEN1 is linked to Alzheimer disease.