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 | Aβ | 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 |