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Review
. 2017 Jun 13;9(1):42.
doi: 10.1186/s13195-017-0268-4.

Stem cell models of Alzheimer's disease: progress and challenges

Charles Arber  1 , Christopher Lovejoy  1 , Selina Wray  2
Affiliations
Review

Stem cell models of Alzheimer's disease: progress and challenges

Charles Arber et al. Alzheimers Res Ther. .

Abstract

A major challenge to our understanding of the molecular mechanisms of Alzheimer's disease (AD) has been the lack of physiologically relevant in vitro models which capture the precise patient genome, in the cell type of interest, with physiological expression levels of the gene(s) of interest. Induced pluripotent stem cell (iPSC) technology, together with advances in 2D and 3D neuronal differentiation, offers a unique opportunity to overcome this challenge and generate a limitless supply of human neurons for in vitro studies. iPSC-neuron models have been widely employed to model AD and we discuss in this review the progress that has been made to date using patient-derived neurons to recapitulate key aspects of AD pathology and how these models have contributed to a deeper understanding of AD molecular mechanisms, as well as addressing the key challenges posed by using this technology and what progress is being made to overcome these. Finally, we highlight future directions for the use of iPSC-neurons in AD research and highlight the potential value of this technology to neurodegenerative research in the coming years.

Keywords: 3D cerebral organoids; Alzheimer’s disease; Induced pluripotent stem cells; Neuronal differentiation.

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Figures

Fig. 1
Fig. 1
Stem cell applications. Schematic to depict the potential applications of stem cell technology. Patient material is reprogrammed to iPSCs via the four reprogramming genes. Relevant advantages and disadvantages of the subsequent differentaition to cortical neurons via 2D and 3D methods are discussed. Finally, applications for stem cell-derived neurons are depicted, namely drug screening, investigating disease mechanisms, in vivo transplantation of neuronal material to model organisms as well as the potential for cell therapy
See this image and copyright information in PMC

References

    1. World Alzheimer Report 2016. https://www.alz.co.uk/research/WorldAlzheimerReport2016.pdf.
    1. Morrissette DA, Parachikova A, Green KN, LaFerla FM. Relevance of transgenic mouse models to human Alzheimer disease. J Biol Chem. 2009;284:6033–7. doi: 10.1074/jbc.R800030200. - DOI - PubMed
    1. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72. doi: 10.1016/j.cell.2007.11.019. - DOI - PubMed
    1. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20. doi: 10.1126/science.1151526. - DOI - PubMed
    1. Park I-H, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, et al. Disease-specific induced pluripotent stem cells. Cell. 2008;134:877–86. doi: 10.1016/j.cell.2008.07.041. - DOI - PMC - PubMed