A Human Neuron/Astrocyte Co-culture to Model Seeded and Spontaneous Intraneuronal Tau Aggregation

Kevin Llewelyn Batenburg, Susan Karijn Rohde, Paulien Cornelissen-Steijger, Nicole Breeuwsma, Vivi Majella Heine, Wiep Scheper

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Communication and contact between neurons and astrocytes is important for proper brain physiology. How neuron/astrocyte crosstalk is affected by intraneuronal tau aggregation in neurodegenerative tauopathies is largely elusive. Human induced pluripotent stem cell (iPSC)-derived neurons provide the opportunity to model tau pathology in a translationally relevant in vitro context. However, current iPSC models inefficiently develop tau aggregates, and co-culture models of tau pathology have thus far utilized rodent astrocytes. In this article, we describe the co-culture of human iPSC-derived neurons with primary human astrocytes in a 96-well format compatible with high-content microscopy. By lentiviral overexpression of different mutated tau variants, this protocol can be flexibly adapted for the efficient induction of seeded or spontaneous tau aggregation. We used this novel co-culture model to identify cell type–specific disease mechanisms and to provide proof of concept for intervention by antisense therapy. These results show that this human co-culture model provides a highly translational tool for target discovery and drug development for human tauopathies.

Original languageEnglish
Article numbere900
Pages (from-to)e900
JournalCurrent protocols
Volume3
Issue number10
DOIs
Publication statusPublished - 1 Oct 2023

Keywords

  • astrocytes
  • co-culture
  • induced pluripotent stem cell
  • neurons
  • tau pathology

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