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Table 1 iPSCs-based AD modeling

From: Induced pluripotent stem cells in Alzheimer’s disease: applications for disease modeling and cell-replacement therapy

Cell type

AD models

Phenotypes

Significance

Ref

FAD-iPSCs

Fibroblasts of FAD patient with mutations in PS1 and PS2

FAD-iPSCs-derived neurons have increased Aβ42 secretion; responds to γ-secretase inhibitors and modulators

Recapitulating the molecular pathogenesis of mutant PS; identification and validation of candidate drugs

[67]

FAD- and SAD-iPSCs

Fibroblasts of FAD patient with mutations in APP; sporadic AD

AD-iPSCs-derived neurons exhibited higher levels of Aβ, pTau, and active GSK-3β; β-secretase inhibitors caused significant reductions in pTau and active GSK-3β levels

The first SAD iPSC model; Demonstrating the direct relationship between APP processing in GSK-3β activation and tau phosphorylation

[68]

AD-iPSCs

Fibroblasts from AD patient

AD-specific iPSCs lines

Exploring AD pathologies; screening new drugs and therapeutic regimens

[70]

AD-iPSCs

Fibroblast of Down syndrome patients

Neurons generated from Down syndrome patients-iPSCs developed AD pathologies

Recapitulating AD pathogenic process including Aβ42 and hyperphosphorylated tau

[71]

FAD-iPSCs

PSEN1 mutant fibroblasts

produced greater ratios of Aβ42 to Aβ40; 14 genes differentially-regulated

Identify novel candidate genes during AD pathology

[72]

FAD-iPSCs

Human dermal fibroblasts

Aβ oligomers accumulation; elevated endoplasmic reticulum (ER) and oxidative stress;

Illustrating how patient-specific iPSCs can be useful for analyzing AD pathogenesis and evaluating drugs.

[73]

SAD-iPSCs

FAD-iPSCs

Human fibroblast carrying APP mutation (V717I)

Increased APP expression and levels of APPsβ, Aβ; increased Aβ42 and Aβ38; increase in levels of total and phosphorylated Tau

Demonstrating the direct casual relationship between elevated Aβ and hyperphosphorylated tau using Aβ neutralizing antibodies, for the first time;

[74]

Providing a model system for testing therapeutic strategies in the cell types most relevant to disease processes