Skip to main content

Cortical Differentiation of Human Pluripotent Cells for In Vitro Modeling of Alzheimer’s Disease

  • Protocol

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1303))

Abstract

Stem cell models of Alzheimer’s disease provide an opportunity to study the mechanisms underlying disease pathology at a resolution that is not possible in animal models. Furthermore, the ability to reprogram patient somatic cells to a pluripotent state ensures that the disease can be investigated in the correct genetic context. Here, we describe the directed differentiation of human pluripotent cells to cortical progenitors by recapitulating key developmental signaling events in vitro. Over a timeframe that mirrors human development, these progenitors give rise to functional lower and upper layer neurons. We also describe biochemical and imaging based methods to analyse key APP and Tau phenotypes in neurons generated from pluripotent stem cells from individuals with either monogenic familial Alzheimer’s disease or Down’s syndrome.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Shi Y, Kirwan P, Smith J et al (2012) Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses. Nat Neurosci 15:477–486, S1

    Article  CAS  PubMed  Google Scholar 

  2. Maroof AM, Keros S, Tyson JA et al (2013) Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells. Cell Stem Cell 12:559–572

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Nicholas CR, Chen J, Tang Y et al (2013) Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12:573–586

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Israel MA, Yuan SH, Bardy C et al (2012) Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482:216–220

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Shi Y, Kirwan P, Smith J et al (2013) A human stem cell model of early Alzheimer’s disease pathology in Down syndrome. Sci Transl Med 4:124ra29

    Google Scholar 

  6. Qiang L, Fujita R, Yamashita T et al (2011) Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146:359–371

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  8. Park IH, Arora N, Huo H et al (2008) Disease-specific induced pluripotent stem cells. Cell 134:877–886

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Yagi T, Ito D, Okada Y, Akamatsu W et al (2011) Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Hum Mol Genet 20:4530–4539

    Article  CAS  PubMed  Google Scholar 

  10. Kondo T, Asai M, Tsukita K et al (2013) Modeling Alzheimer’s disease with iPSCs reveals stress phenotypes associated with intracellular Abeta and differential drug responsiveness. Cell Stem Cell 12:487–496

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Work in the lab of FJL is supported by the Wellcome Trust, Alzheimer’s Research UK, the Medical Research Council and the EU Innovative Medicines Initiative StemBANCC. NS is supported by the Woolf Fisher Trust. FJL is a Wellcome Trust Senior Investigator.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frederick J. Livesey .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Saurat, N.G., Livesey, F.J., Moore, S. (2016). Cortical Differentiation of Human Pluripotent Cells for In Vitro Modeling of Alzheimer’s Disease. In: Castrillo, J., Oliver, S. (eds) Systems Biology of Alzheimer's Disease. Methods in Molecular Biology, vol 1303. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2627-5_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2627-5_16

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2626-8

  • Online ISBN: 978-1-4939-2627-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics