Quantitative propagation of assembled human Tau from Alzheimer's disease brain in microfluidic neuronal cultures

Antigoni Katsikoudi, Elena Ficulle, Annalisa Cavallini, Gary Sharman, Amelie Guyot, Michele Zagnoni, Brian J. Eastwood, Michael Hutton, Suchira Bose

Research output: Contribution to journalArticle

5 Downloads (Pure)

Abstract

Tau aggregation and hyperphosphorylation is a key neuropathological hallmark of Alzheimer's disease (AD), and the temporospatial spread of Tau observed during clinical manifestation suggests that Tau pathology may spread along the axonal network and propagate between synaptically connected neurons. Here, we have developed a cellular model that allows the study of human AD-derived Tau propagation from neuron to neuron using microfluidic devices. We show by using high-content imaging techniques and an in-house developed interactive computer program that human AD-derived Tau seeds rodent Tau that propagates trans-neuronally in a quantifiable manner in a microfluidic culture model. Moreover, we were able to convert this model to a medium-throughput format allowing the user to handle 16 two-chamber devices simultaneously in the footprint of a standard 96-well plate. Furthermore, we show that a small molecule inhibitor of aggregation can block the trans-neuronal transfer of Tau aggregates, suggesting that the system can be used to evaluate mechanisms of Tau transfer and find therapeutic interventions.

Original languageEnglish
Pages (from-to)13079-13093
Number of pages15
JournalJournal of Biological Chemistry
Volume295
Issue number37
Early online date22 Jul 2020
DOIs
Publication statusPublished - 11 Sep 2020

Keywords

  • microtubule
  • neurodegeneration
  • protein aggregation
  • Tau protein
  • tauopathy
  • drug screening
  • microfluidics
  • Alzheimer disease
  • neurodegenerative disease
  • neuron

Fingerprint Dive into the research topics of 'Quantitative propagation of assembled human Tau from Alzheimer's disease brain in microfluidic neuronal cultures'. Together they form a unique fingerprint.

  • Cite this

    Katsikoudi, A., Ficulle, E., Cavallini, A., Sharman, G., Guyot, A., Zagnoni, M., Eastwood, B. J., Hutton, M., & Bose, S. (2020). Quantitative propagation of assembled human Tau from Alzheimer's disease brain in microfluidic neuronal cultures. Journal of Biological Chemistry, 295(37), 13079-13093. https://doi.org/10.1074/jbc.RA120.013325