A 3D human neural cell culture system for modeling Alzheimer's disease
Open accessAbstract
Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer's disease (AD), because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel 3D culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of amyloid-β (Aβ) and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix and the analysis of AD pathogenesis. The 3D culture generation takes 1-2 d. The aggregation of Aβ is observed after 6 weeks of differentiation, followed by robust tau pathology after 10-14 weeks.
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Development of a 3D culture of human neural stem cells transfected with APPK670N/M671L/V717I and PS1ΔE9 in Matrigel scaffolding resulted in extracellular aggregation of Aβ into plaques and intracellular aggregation of tau in dystrophic neurites and the cell soma.
“It was recently shown that development of a 3D culture of human neural stem cells transfected with APPK670N/M671L/V717I and PS1ΔE9 in Matrigel scaffolding resulted in the extracellular aggregation of Aβ into plaques and the intracellular aggregation of tau in dystrophic neurites and the cell soma [23, 77].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [77]
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References 45 · Cited by 269
Research works printed but not linked: 1
- [43]Choi SH A three-dimensional human neural cell culture model of Alzheimer’s disease Nature 515 274 278 2014 25307057 PMC4366007
- Authors
- Kim, Y. H., Choi, S. H., D'Avanzo, C., Hebisch, M., Sliwinski, C., Bylykbashi, E., Washicosky, K. J., Klee, J. B., Brüstle, O., Tanzi, R. E., & Kim, D. Y.
- Affiliations
- Harvard University (US)
- University of Bonn (DE)
- Corresponding author
- Tanzi, Rudolph E
- Kim, Doo Yeon
- Venue
- Nature Protocols
- Published
- 2015-06-11
- Volume
- 10
- Issue
- 7
- Pages
- 985-1006
- ISSN
- 1750-2799 (ISSN-L)
- 1754-2189
- PMC
- PMC4499058
- OpenAlex
- W1837455343
- Cited by
- 269
- References
- 45
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 19 · 2023: 22 · 2022: 26 · 2021: 31 · 2020: 22 · 2019: 30 · 2018: 32 · 2017: 23 · 2016: 19 · 2015: 4
- FWCI
- 19.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Protocols (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Funders
- National Institute on Aging (5P01 AG15379, P01AG015379, R21AG031483, RF1AG048080, P50AG005134, R01AG014713, P30AG062421)
- National Institute of Mental Health (R37MH060009)
- National Institute of Neurological Disorders and Stroke (P30NS04776, P30NS045776)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Alzheimer's disease, human neural progenitor cells, familial Alzheimer's disease mutations, amyloid-beta aggregation, tau hyperphosphorylation, Matrigel, disease modeling, neuronal differentiation
- MeSH terms
- Alzheimer Disease, Cell Differentiation, Cell Line, Humans, Models, Neurological, Mutation, Amyloid beta-Peptides, tau Proteins, Cell Culture Techniques, Neural Stem Cells, Protein Aggregation, Pathological
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