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Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells

Developing cellular models of sporadic Alzheimer’s disease (sAD) is challenging due to the unknown initiator of disease onset and the slow disease progression that takes many years to develop in vivo. The use of human induced pluripotent stem cells (iPSCs) has revolutionised the opportunities to mod...

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Autores principales: Rowland, Helen A., Hooper, Nigel M., Kellett, Katherine A. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267251/
https://www.ncbi.nlm.nih.gov/pubmed/30387070
http://dx.doi.org/10.1007/s11064-018-2663-z
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author Rowland, Helen A.
Hooper, Nigel M.
Kellett, Katherine A. B.
author_facet Rowland, Helen A.
Hooper, Nigel M.
Kellett, Katherine A. B.
author_sort Rowland, Helen A.
collection PubMed
description Developing cellular models of sporadic Alzheimer’s disease (sAD) is challenging due to the unknown initiator of disease onset and the slow disease progression that takes many years to develop in vivo. The use of human induced pluripotent stem cells (iPSCs) has revolutionised the opportunities to model AD pathology, investigate disease mechanisms and screen potential drugs. The majority of this work has, however, used cells derived from patients with familial AD (fAD) where specific genetic mutations drive disease onset. While these provide excellent models to investigate the downstream pathways involved in neuronal toxicity and ultimately neuronal death that leads to AD, they provide little insight into the causes and mechanisms driving the development of sAD. In this review we compare the data obtained from fAD and sAD iPSC-derived cell lines, identify the inconsistencies that exist in sAD models and highlight the potential role of Aβ clearance mechanisms, a relatively under-investigated area in iPSC-derived models, in the study of AD. We discuss the development of more physiologically relevant models using co-culture and three-dimensional culture of iPSC-derived neurons with glial cells. Finally, we evaluate whether we can develop better, more consistent models for sAD research using genetic stratification of iPSCs and identification of genetic and environmental risk factors that could be used to initiate disease onset for modelling sAD. These considerations provide exciting opportunities to develop more relevant iPSC models of sAD which can help drive our understanding of disease mechanisms and identify new therapeutic targets.
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spelling pubmed-62672512018-12-11 Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells Rowland, Helen A. Hooper, Nigel M. Kellett, Katherine A. B. Neurochem Res Overview Developing cellular models of sporadic Alzheimer’s disease (sAD) is challenging due to the unknown initiator of disease onset and the slow disease progression that takes many years to develop in vivo. The use of human induced pluripotent stem cells (iPSCs) has revolutionised the opportunities to model AD pathology, investigate disease mechanisms and screen potential drugs. The majority of this work has, however, used cells derived from patients with familial AD (fAD) where specific genetic mutations drive disease onset. While these provide excellent models to investigate the downstream pathways involved in neuronal toxicity and ultimately neuronal death that leads to AD, they provide little insight into the causes and mechanisms driving the development of sAD. In this review we compare the data obtained from fAD and sAD iPSC-derived cell lines, identify the inconsistencies that exist in sAD models and highlight the potential role of Aβ clearance mechanisms, a relatively under-investigated area in iPSC-derived models, in the study of AD. We discuss the development of more physiologically relevant models using co-culture and three-dimensional culture of iPSC-derived neurons with glial cells. Finally, we evaluate whether we can develop better, more consistent models for sAD research using genetic stratification of iPSCs and identification of genetic and environmental risk factors that could be used to initiate disease onset for modelling sAD. These considerations provide exciting opportunities to develop more relevant iPSC models of sAD which can help drive our understanding of disease mechanisms and identify new therapeutic targets. Springer US 2018-11-01 2018 /pmc/articles/PMC6267251/ /pubmed/30387070 http://dx.doi.org/10.1007/s11064-018-2663-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Overview
Rowland, Helen A.
Hooper, Nigel M.
Kellett, Katherine A. B.
Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells
title Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells
title_full Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells
title_fullStr Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells
title_full_unstemmed Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells
title_short Modelling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells
title_sort modelling sporadic alzheimer’s disease using induced pluripotent stem cells
topic Overview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267251/
https://www.ncbi.nlm.nih.gov/pubmed/30387070
http://dx.doi.org/10.1007/s11064-018-2663-z
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