The recently established technology of creating human blood cell-derived induced pluripotent stem cells (iPSC) presents an additional opportunity for improving in vitro models of AD. Several studies demonstrate the importance of this technology. Israel et al. created iPSC lines from two normal subjects, two sporadic AD (sAD1 and sAD2), and two familial AD patients [15]. Human differentiated neurons from two familial AD patients and sAD2 showed very high levels of Aβ1–40, phosphorylated Tau (pTau at Thr 231) and active GSK3β. Importantly, Israel found that levels of Aβ, pTau and active GSK3β can be reduced in these neurons by BACE1 inhibitors, but not γ-secretase inhibitors, indicating a direct relationship between the APP C-terminal fragment (CTF) and GSK3β activation/Tau phosphorylation [15]. Another study compared cultured neurons differentiated from iPSC lines of familial AD patients carrying a mutant PS1 or PS2 gene to those from control, cognitively normal centenarians [16] and found an increased ratio of Aβ42/Aβ40. iPSC-differentiated human neurons have been used to demonstrate accumulation and aggregation of intraneuronal Tau after Tau oligomers were internalized [17]. Similarly, oligomeric Aβ is shown to
