Efficient propagation of misfolded tau between individual neurons occurs in absence of degeneration

Grace I Hallinan, Mariana Vargas-Caballero, Jonathan West, Katrin Deinhardt

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Jul 30, 2018
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Received: 15th July 18

In Alzheimer’s disease, misfolded tau protein propagates through the brain in a prion-like manner along connected circuits. Tauopathy correlates with significant neuronal death, but the links between tau aggregation, propagation, neuronal dysfunction and death remain poorly understood, and the direct functional consequences for the neuron containing the tau aggregates are unclear. Here, by monitoring individual neurons within a minimal circuit, we demonstrate that misfolded tau efficiently spreads from presynaptic to postsynaptic neurons. Within postsynaptic cells, tau aggregates initially in distal axons, while proximal axons remain free of tau pathology. In the presence of tau aggregates neurons display axonal transport deficits, but remain viable and electrically competent. This shows that misfolded tau species are not immediately toxic to neurons, and suggests that propagation of misfolded tau is an early event in disease, occurring prior to neuronal dysfunction and cell death.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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Nature Communications

Nature Research, Springer Nature

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