An in vitro model for studying tau aggregation using lentiviral-mediated transduction of human neurons

Brent Aulston, Qing Liu, Patrick Reilly, Shauna H. Yuan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Aberrant aggregation of the protein tau is pathogenically involved in a number of neurodegenerative diseases, including Alzheimer’s disease (AD). Although mouse models of tauopathy have provided a valuable resource for investigating the neurotoxic mechanisms of aggregated tau, it is becoming increasingly apparent that, due to interspecies differences in neurophysiology, the mouse brain is unsuitable for modeling the human condition. Advances in cell culture methods have made human neuronal cultures accessible for experimental use in vitro and have aided in the development of neurotherapeutics. However, despite the adaptation of human neuronal cell cultures, in vitro models of human tauopathy are not yet widely available. This protocol describes a cellular model of tau aggregation in which human neurons are transduced with lentiviralderived vectors that code for pathogenically mutated tau fused to a yellow fluorescent protein (YFP) reporter. Transduced cultures produce tau aggregates that stain positively for thioflavin and display markers of neurotoxicity, such as decreased axonal length and increased lysosomal volume. This procedure may be a useful and cost-effective model for studying human tauopathies.

Original languageEnglish (US)
Article numbere59433
JournalJournal of Visualized Experiments
Volume2019
Issue number147
DOIs
StatePublished - May 2019
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank Dr. Peter Davies at Albert Einstein College of Medicine for supplying PHF-1 and CP13 antibodies and Dr. Marc Diamond at the University of Texas, Southwestern, for providing the tau constructs. This work was supported by grants from the Alzheimer’s Association (NIRG-14-322164) to S.H.Y. and from the California Institute for Regenerative Medicine (TB1-01193) to P.R.

Funding Information:
The authors would like to thank Dr. Peter Davies at Albert Einstein College of Medicine for supplying PHF-1 and CP13 antibodies and Dr. Marc Diamond at the University of Texas, Southwestern, for providing the tau constructs. This work was supported by grants from the Alzheimer?s Association (NIRG-14-322164) to S.H.Y. and from the California Institute for Regenerative Medicine (TB1-01193) to P.R.

Publisher Copyright:
© 2019 Journal of Visualized Experiments.

Keywords

  • Alzheimer’s disease
  • Frontotemporal dementia
  • Issue 147
  • Lentivirus
  • Neural stem cells
  • Neurodegeneration
  • Neuron
  • Neuroscience
  • Tau
  • Tauopathy

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