Cited by 482Pluripotent Stem Cells ResearchAlzheimer's disease research and treatmentsNeurogenesis and neuroplasticity mechanisms

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Modeling Alzheimer’s disease with iPSC-derived brain cells

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Penney, Jay, Ralvenius, William T., Tsai, Li-Huei·2020·Molecular Psychiatry

DOI 10.1038/s41380-019-0468-3PMC PMC6906186

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Abstract

Alzheimer's disease is a devastating neurodegenerative disorder with no cure. Countless promising therapeutics have shown efficacy in rodent Alzheimer's disease models yet failed to benefit human patients. While hope remains that earlier intervention with existing therapeutics will improve outcomes, it is becoming increasingly clear that new approaches to understand and combat the pathophysiology of Alzheimer's disease are needed. Human induced pluripotent stem cell (iPSC) technologies have changed the face of preclinical research and iPSC-derived cell types are being utilized to study an array of human conditions, including neurodegenerative disease. All major brain cell types can now be differentiated from iPSCs, while increasingly complex co-culture systems are being developed to facilitate neuroscience research. Many cellular functions perturbed in Alzheimer's disease can be recapitulated using iPSC-derived cells in vitro, and co-culture platforms are beginning to yield insights into the complex interactions that occur between brain cell types during neurodegeneration. Further, iPSC-based systems and genome editing tools will be critical in understanding the roles of the numerous new genes and mutations found to modify Alzheimer's disease risk in the past decade. While still in their relative infancy, these developing iPSC-based technologies hold considerable promise to push forward efforts to combat Alzheimer's disease and other neurodegenerative disorders.

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Fig. 1 Brain cell types in Alzheimer’s disease. A summary of the major human brain cell types and the alterations they exhibit in ADCC BY · PubMed Central

Fig. 2 Human iPSC differentiation to brain cell types. Somatic cells from patients or healthy individuals can be reprogrammed to iPSCs and subsequently differentiated into all major brain cell types for in vitro studies. Such studies can examine cellular functions as well as how they are impacted by AD hallmark pathologies or AD-linked mutations. Genome editing techniques can be used to introduce or correct AD-linked mutations to examine phenotypes in isogenic backgrounds. 3D and co-culture models allow for examination of interactions occurring between cell types and sub-types to better model processes occurring in vivo. These and developing techniques hold promise for better understanding the relevant pathomechanisms underlying AD, and will hopefully facilitate development of effective therapeutics to combat dementiaCC BY · PubMed Central

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Authors: Penney, J., Ralvenius, W. T., & Tsai, L.-H.
Affiliations: Massachusetts Institute of Technology (US)
Corresponding author: Tsai, Li-Huei
ORCID: Penney, Jay
Ralvenius, William T.
Tsai, Li-Huei
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2019-08-07
Volume: 25
Issue: 1
Pages: 148-167
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/s41380-019-0468-3
PMC: PMC6906186
OpenAlex: W2964627277
Cited by: 471
References: 235
Citations by year: 2026: 54 · 2025: 66 · 2024: 78 · 2023: 84 · 2022: 77 · 2021: 65 · 2020: 41 · 2019: 6
FWCI: 4.18
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Molecular Psychiatry (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
IslandScholar (University of Prince Edward Island) (submittedVersion)
Funders: National Science Foundation
Cure Alzheimer's Fund
Robert A. and Renee E. Belfer Family Foundation
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (177920)
National Institutes of Health (NS051874)
National Institute on Aging (RF1AG054012)
National Institute of Neurological Disorders and Stroke (R37NS051874)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: Alzheimer's disease, induced pluripotent stem cells, neurodegeneration, co-culture model, disease modeling, genome editing, Alzheimer's disease risk genes, preclinical research
MeSH terms: Alzheimer Disease, Brain, Cell Differentiation, Humans, Models, Biological, Neurons, Neurodegenerative Diseases, Induced Pluripotent Stem Cells

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Modeling Alzheimer’s disease with iPSC-derived brain cells

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