Alzheimer's in 3D culture: Challenges and perspectives
Open accessAbstract
Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery.
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3D models of Alzheimer's disease offer the complexity of the brain without the ethical constraints of animal models.
“3D models of AD offer the complexity of the brain without the ethical constraints of animal models [147].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [147]
The section “Why is 3D better than 2D for modeling AD?” says 3D cultures more closely mimic in vivo environments and improve neural network formation, supporting the brain-like modeling part of the claim. The section on challenges says that reconstituting affected brain regions remains difficult, so the paper does not claim these models reproduce the brain’s full complexity. No passage found in our copy addresses ethical constraints of animal models. (LLM, conf=0.86)
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- Authors
- D'Avanzo, C., Aronson, J., Kim, Y. H., Choi, S. H., Tanzi, R. E., & Kim, D. Y.
- Affiliations
- Genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA USA
- Harvard University (US)
- Korea Basic Science Institute (KR)
- Corresponding author
- Kim, Doo Yeon
- Venue
- BioEssays
- Publisher
- Wiley
- Published
- 2015-08-07
- Volume
- 37
- Issue
- 10
- Pages
- 1139-1148
- ISSN
- 0265-9247 (ISSN-L)
- 1521-1878
- PMC
- PMC4674791
- OpenAlex
- W1830876320
- Cited by
- 111
- References
- 15
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 14 · 2023: 8 · 2022: 5 · 2021: 12 · 2020: 18 · 2019: 7 · 2018: 15 · 2017: 8 · 2016: 10 · 2015: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- BioEssays (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Foundation for the National Institutes of Health (1RF1AG048080-01, 5P01AG15379, 5R37MH060009, 2R01AG014713)
- Cure Alzheimer's Fund
- National Research Foundation of Korea (2015M3A9C7030151)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- Alzheimer's disease, 3D cell culture, human neural stem cells, amyloid plaques, neurofibrillary tangles, mouse models of Alzheimer's disease, drug discovery
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Humans, Amyloid beta-Protein Precursor, Cell Culture Techniques, Mice, Neural Stem Cells
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