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Table 1 Summary of studies using genomically unaltered iPSC-derived neurons to investigate AD

From: Stem cell models of Alzheimer’s disease: progress and challenges

Study Mutations investigated Tau γ-Secretase inhibitor β-Secretase inhibitor Other drugs  
Yagi et al. 2011 [62] PSEN1 A246E PSEN2 N141I ↑Aβ42 ↑Aβ42:40   Compound E ↓Aβ   Compound W ↓Aβ42 • New insights into AD
Yahata et al. 2011 [63] Controls    GSI ↓Aβ BSI ↓Aβ NSAID ↓Aβ • Relevant expression of APP and secretase subunits in iPSC-neurons
Israel et al. 2012 [64] APP duplication sAD ↑Aβ40 ↑pTau ↑Activated GSK3β     • Swollen endosomes • sAD variability
Shi et al. 2012 [65] DS ↑Aβ40, ↑Aβ42 Aggregates ↑pTau and redistribution DAPT ↓Aβ    
Kondo et al. 2013 [67] APP E693Δ→ APP V717L→ sAD ↓Aβ40 ↑Aβ42 Aβ oligomer accumulation    ↓Aβ DHA ↓Aβ • Difference effect of two mutations • Intracellular Aβ • UPR and ROS
Woodruff et al. 2013 [76] PSEN1 ΔE9 ↑Aβ42:40   Compound E ↑Aβ42:40 of wild-type neurons    • PSEN1 ΔE9 is dominant negative and does not affect γ-secretase-independent functions
Duan et al. 2014 [68] PSEN1 A246E fAD APOE ↑Aβ42:40   Compound E ↓Aβ40    • APOE4 cells are sensitive to neurotoxic stimuli
Muratore et al. 2014 [71] APP V717I ↑Aβ42:40   DAPT ↓Aβ    • APP mutant cells ↑APP (protein and not RNA), ↑tTau, ↑pTau
Mahairaki et al. 2014 [69] PSEN1 A246E ↑Aβ42:40 ↑sAPPβ   DAPT ↓sAPPβ    • Presence of APP in endosomes
Sproul et al. 2014 [72] PSEN1 A246E PSEN1 M146L ↑Aβ42:40      • Altered gene pathways include NLRP2, ASB9 and NDP
Chang et al. 2015 [74] DS ↑A40 ↑A42 Aggregates ↑tTau ↑pTau DAPT ↓Aβ, ↓tTau ↓pTau   Bdph ↓Aβ, ↓tTau, ↓pTau • Tau mislocalisation
Moore 2015 [75] APP V717I APP duplication PSEN1 ΔI4 PSEN1 Y115C DS ↑A42:40 APP dup unchanged APP (not PSEN1) leads to ↑tTau ↑pTau DAPT and E2012 γ-Secretase and APP are coupled to Tau LY2886721 does not alter Tau   • APP processing and intracellular fragment linked to Tau proteostasis
Hossini 2015 [153] sAD   ↑pTau, ↑activated GSK3β Compound E    • Neurodegenerative gene pathways downregulated
Raja 2016 [78] APP duplication PSEN1 M136I PSEN1 A 264E ↑Aβ Aggregates ↑pTau Compound E ↓Aβ and ↓pTau BACE-1i ↓Aβ and ↓pTau   
  1. Abbreviations: Bdph N-butylidenephthalide, BSI β-secretase inhibitor, DHA docosahexaenoic acid, DS Down’s syndrome, GSI γ-secretase inhibitor, NSAID non-steroidal anti inflammatory drug, pTau phosphorylated Tau, ROS reactive oxygen species, sAPPβ soluble APP (β-secretase pathway), tTau total Tau, UPR unfolded protein response