In contrast with previous studies, where Aβ deposition in a 3D ECM was only observed when iPSC-derived neurons were expressing APP and/or presenilin 1 with familial AD associated mutations [20,52], the two iPSC lines used in the present study are derived from individuals without AD and were not genetically modified either to overexpress APP or with mutations in APP or the presenilins associated with familial AD. Here, PSEN1 is linked to Alzheimer disease.