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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]
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