Cited by 143Alzheimer's disease research and treatmentsPluripotent Stem Cells ResearchDementia and Cognitive Impairment Research

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

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Arber, Charles, Lovejoy, Christopher, Wray, Selina·2017·Alzheimer's Research & Therapy

DOI 10.1186/s13195-017-0268-4PMC PMC5470327

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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.

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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 therapyCC BY · PubMed Central

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Steg, L. C., Shireby, G. L., Imm, J. L., Davies, J. P., Franklin, A., Flynn, R., Namboori, S. C., Bhinge, A., Jeffries, A. R., Burrage, J., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14853114
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Authors: Arber, C., Lovejoy, C., & Wray, S.
Affiliations: UCL Queen Square Institute of Neurology (GB)
Corresponding author: Wray, Selina
ORCID: Arber, Charles
Lovejoy, Christopher
Wray, Selina
Venue: Alzheimer's Research & Therapy
Publisher: Springer Science and Business Media LLC
Published: 2017-06-13
Volume: 9
Issue: 1
Pages: 42-42
ISSN: 1758-9193 (ISSN-L)
DOI: 10.1186/s13195-017-0268-4
PMC: PMC5470327
OpenAlex: W2624768339
Cited by: 143
References: 157
Citations by year: 2026: 7 · 2025: 8 · 2024: 13 · 2023: 10 · 2022: 14 · 2021: 19 · 2020: 26 · 2019: 26 · 2018: 19
FWCI: 2.38
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Alzheimer s Research & Therapy (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
UCL Discovery (University College London) (submittedVersion)
Funders: Alzheimer’s Research UK
National Centre for the Replacement, Refinement and Reduction of Animals in Research
National Institute for Health Research
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, induced pluripotent stem cells, iPSC-derived neurons, patient-derived neurons, neuronal differentiation, in vitro disease model, neurodegeneration
MeSH terms: Alzheimer Disease, Animals, Cells, Cultured, Disease Models, Animal, Humans, Organoids, Tissue Engineering, Induced Pluripotent Stem Cells, Neural Stem Cells, Batch Cell Culture Techniques

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

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