cascade of events leading to cell death and continuous brain degeneration. The cells were differentiated into deep layer cortical pyramidal neurons and GABAergic interneurons; and upon longer cultivation, these cells exhibited action potential generation and excitatory and inhibitory synapses. Yet, most interesting was that these AD-derived neurons were very susceptible to Aβ synaptotoxicity (Nieweg et al., 2015). In a study on epigenetic characterization of iPSCs DA differentiated neurons, there was significant difference in global gene expression and DNA methylation as compared to the in vivo DA cells (Roessler et al., 2014). Therefore, epigenetic changes seem to leave their mark on the genome even beyond de-differentiation and this is mainly considered a limitation for applying iPSCs in human therapies. Since the cells in these experiments were needed to be passaged and tested at several time points, trans-differentiation does not seem to be the proper method for such application. Yet, all these models offer valuable insight about AD and understanding its progression and further designing therapeutics.
