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 |