APP and familial Alzheimer disease: For a more encompassing and complete review on brain organoid protocols, current advances, and limitations, refer to Papaspyropoulos et al. [147] A scaffold-free 3D model generated from fibroblasts of controls and patients with fAD, the result of a duplication in APP or a PSEN1 mutation, resulted in elevated levels of Aβ and p-tau in organoids from fAD cultures compared to controls [148].