APP and familial Alzheimer disease: Recently, more complex 3D arrangements of cells resembling human brain tissue, termed brain organoids, which use pluripotent stem cells derived from FAD patients (harboring amyloid precursor protein–APP-duplication or presenilin1 –PSEN1-mutation), have shown the spontaneous emergence of hallmark AD pathologies such as increases in Aβ42 soluble fragment secretion and amyloid aggregation, when compared to control organoids [17,18].