MAPT and Alzheimer disease: However, Choi et al. (2014) provided evidence that, in a 3D human neural stem cells (NSCs) culture system, the accumulation of Aβ-os precedes any p-Tau/NFTs materialization thereby validating the “amyloid cascade hypothesis.” Bilousova et al. (2016) confirmed that this Aβ-os ⇒ p-Tau sequence occurs also in advanced AD stages, strengthening the view that an anti-amyloid therapy must be started in advance of the tauopathy onset.