Human induced pluripotent stem cells as a research tool in Alzheimer's disease

Abstract

Human-induced pluripotent stem cells (iPSCs) offer a novel, timely approach for investigating the aetiology of neuropsychiatric disorders. Although we are starting to gain more insight into the specific mechanisms that cause Alzheimer's disease and other forms of dementia, this has not resulted in therapies to slow the pathological processes. Animal models have been paramount in studying the neurobiological processes underlying psychiatric disorders. Nonetheless, these human conditions cannot be entirely recapitulated in rodents. Human cell models derived from patients' cells now offer new hope for improving our understanding of the early molecular stages of these diseases, through to validating therapeutics. The impact of dementia is increasing, and a new model to investigate the early stages of this disease is heralded as an essential, new platform for translational research. In this paper, we review current literature using iPSCs to study Alzheimer's disease, describe drug discovery efforts using this platform, and discuss the future potential for this technology in psychiatry research.

Keywords: Alzheimer's disease; cell models; dementia; disease modelling; induced pluripotent stem cells.

Figures

Figure 1

Adult somatic cells obtained from the root shaft of scalp hair are reprogrammed into iPSCs, which can then be differentiated into specific cell types. Cells from multiple sources can be utilised for reprogramming with the ‘Yamanaka factors’, with keratinocytes providing a non-invasive option. iPSCs can be differentiated into any cell type, with the SMAD inhibition protocol developed by Shi et al. (2012a) producing cortical neurons. These neurons can be used for studying disease processes or drug screening.

Figure 2

The increase in journal articles on Alzheimer’s disease using iPSCs. Generated from Web of Sciene citation report using search from ‘alzheimer’s included pluripotent stem cell’. A. Number of published articles by year. B. Number of citations of all articles per year. Citation Report graphic is derived from Thomson Reuters Web of Science, Copyright THOMSON REUTERS ® 201_. All rights reserved. (Date accessed 20/03/17.)