Induced pluripotent stem cell-derived astroglia: A new tool for research towards the treatment of alzheimer’s disease

Abstract

Despite over a century of research into Alzheimer’s disease (AD), progress in understanding the complex aetiology has been hindered, in part, by a lack of human, disease relevant, cellular models, reflected in an inability to translate results from animal studies to successful human therapies. Induced pluripotent stem cell (iPSC) technology, in which somatic cells are reprogrammed to pluripotent stem cells, creates an ideal physiologically relevant model as they maintain the genetic identity of the donor. These iPSCs can self-renew indefinitely in vitro and have the capacity to differentiate into any cell type, opening up new discovery and therapeutic opportunities. Despite a plethora of publications indicating the generation and utility of iPSC-derived neurones for disease modelling to date, in comparison only a limited number of studies have described generation of enriched astroglia from patients with early- or late-stage onset of AD. We recently reported that iPSC-astroglia derived from these patients are capable of mimicking a wide variety of deficits in homeostatic molecular cascades, intimately associated with AD, that are routinely observed in vivo. This review examines the opportunities and limitations of this innovative technology in the context of AD modelling and uses for preclinical discovery to improve our success for an efficacious therapeutic outcome.