gamma-secretase modulation (Mertens et al., 2013). This is in contrast to results from transgenic cell lines and mouse models, indicating the need to validate compound efficacy directly in the human cell type affected by disease. Second, Brüstle developed an hiPSC-based model of the polyglutamine disorder Machado-Joseph disease (spinocerebellar ataxia type 3) to illustrate how the earliest steps in protein aggregation can be modeled in patient-derived cells (Koch et al., 2011). Aggregates of ataxin-3 were observed specifically in hiPSC-derived neurons, but not in primary patient fibroblasts, hiPSCs, or hiPSC-derived glial cells. His group’s findings indicate that pronounced neuronal intranuclear inclusions are specific to neurons and help to explain the reason for neuron-specific degeneration in this disease. Finally, he also discussed latest developments in studying in vivo integration and connectivity phenotypes of transplanted iPSC-derived neurons with rabies-virus-based monosynaptic tracing and light sheet microscopy of whole-brain preparations.
