The importance of a 3D environment in recreating important AD clinical characteristics is highlighted by the observation that human neural progenitor cells overexpressing FAD APP and PSEN1 mutations have an increased Aβ42/Aβ40 ratio that encourages the production of neurofibrillary tangles in a 3D culture system [67, 68]. The gene discussed is PSEN1; the disease is Alzheimer disease.