Another important consideration with the use of iPSCs in disease modelling is that these cells and their differentiated derivatives often resemble those of foetal origin (Hrvatin et al. 2014), and therefore the age of onset of any disease becomes relevant. Indeed, iPSC-derived neurons initially differentiate into an immature state and can require months in culture before they become electrophysiologically active. This complicates analysis of diseases such as neurodegeneration which only show effects late in life. Several strategies exist to circumvent this issue, at least to some extent. Often, rare, early-onset, familial mutations are associated with many normally polygenic late-onset diseases, and these can be useful models to study phenotypes associated with such diseases in general. One example of this is a triplication of a large region including the SNCA locus that leads to an early-onset Parkinson’s disease phenotype (Devine et al. 2011). iPSC-derived dopaminergic neurons derived from these patients show molecular phenotypes characteristic of the disease, suggesting that such pathological events can be detected and monitored (Chung et al. 2013). An alternative strategy is to accelerate ageing or disease progression
