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

The Journal of Biological Chemistry
Antigoni KatsikoudiSuchira Bose

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.

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Citations

Jul 28, 2021·PLoS Computational Biology·Justin TorokAshish Raj
Oct 15, 2020·ACS Chemical Neuroscience·Benjamin J BellBarbara S Slusher

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Methods Mentioned

BETA
AlphaScreen
transgenic

Software Mentioned

Cell Counter
Cell
GraphPad Prism
Harmony
AlphaScreen
JMP
Operetta

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