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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