Capturing Alzheimer's disease genomes with induced pluripotent stem cells: prospects and challenges

A crucial limitation to our understanding of Alzheimer's disease (AD) is the inability to test hypotheses on live, patient-specific neurons. Patient autopsies are limited in supply and only reveal endpoints of disease. Rodent models harboring familial AD mutations lack important pathologies, and animal models have not been useful in modeling the sporadic form of AD because of complex genetics. The recent development of induced pluripotent stem cells (iPSCs) provides a method to create live, patient-specific models of disease and to investigate disease phenotypes in vitro. In this review, we discuss the genetics of AD patients and the potential for iPSCs to capture the genomes of these individuals and generate relevant cell types. Specifically, we examine recent insights into the genetic fidelity of iPSCs, advances in the area of neuronal differentiation, and the ability of iPSCs to model neurodegenerative diseases.