How to study human dementia in a dish?

High-content assays for human neurons: a proof-of-concept study into neuronal network impairments in frontotemporal dementia.

Dementia is increasingly a socio-economic problem for which no effective treatment exists yet. New scientific insights show that the early cognitive problems that arise in dementia are mainly due to subtle changes in the way nerve cells communicate with each other and work together in so-called nerve networks. Effective disadvantage should therefore focus primarily on these early changes in nerve networks.

In this project, an assay was developed based on human nerve cells that can be used to measure morphological and functional changes in nerve networks in an automated way. To validate the assay, a cell model for frontotemporal dementia (FTD) was developed. In the assay, these cells show decreases in nerve cell survival and in the number of synaptic connections between nerve cells. With this cell model in hand, and with the developed assay to accurately measure changes in nerve network connectivity, it is now possible to screen for substances that can restore FTD-related changes in nerve networks.

Summary

A fully automated microscopy and image analyses pipeline was developed for cultured human neurons. The findings show that human neurons with a molecular alteration that is specific for frontotemporal dementia show changes in connectivity that may be an important early causal factor in the disease.

Technology Readiness Level (TRL)

2 - 4

Time period

18 months

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