The Use of Patient-Derived Induced Pluripotent Stem Cells for Alzheimer's Disease Modeling.

ABSTRACT

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by a progressive deterioration in multiple facets of cognitive function. As the average age of the population rises, AD poses a massive current and future healthcare threat. Today, there is no cure for AD nor well-established interventions to slow progression, and treatment is largely symptomatic. The failure rate for new drugs in clinical trials has remained high, pointing out a critical need for better disease modeling that can enhance our understanding of basic disease pathophysiology, leading to better drug discovery and preclinical validation. The advent of induced pluripotent stem cells (iPSCs) has allowed researchers access to an unlimited supply of patient cells that can be differentiated into a neural fate, allowing for modeling of neurological disorders such as AD. This development has propelled AD research and presents opportunities to produce more accurate AD models to facilitate research into pathophysiology as well as drug screening and development. In this review, we conduct an in-depth assessment of the literature to identify the majority of work to date on patient-derived iPSCs. We outline research into both the familial and sporadic forms of the disease, as well as modern methods of modeling the disease three-dimensionally. Finally, we identify challenges to be addressed and areas of further research for iPSC modeling of AD.