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Tau misfolding efficiently propagates between individual intact hippocampal neurons

Tau misfolding efficiently propagates between individual intact hippocampal neurons
Tau misfolding efficiently propagates between individual intact hippocampal neurons
Neurofibrillary tangles, formed of misfolded, hyperphosphorylated tau protein, are a pathological hallmark of several neurodegenerations, including Alzheimer's disease. Tau pathology spreads between neurons and propagates misfolding in a prion-like manner throughout connected neuronal circuits. Tauopathy is accompanied by significant neuronal death, but the relationships between initial tau misfolding, propagation across connected neurons and cytotoxicity remain unclear. In particular the immediate functional consequence of tau misfolding for the individual neuron is not well understood. Here, using microfluidic devices to recreate discretely organized neuronal connections, we show that the spread and propagation of misfolded tau between individual murine neurons is rapid and efficient; it occurs within days. The neurons containing and propagating tau pathology display selective axonal transport deficits but remain viable and electrically competent. Therefore, we demonstrate that seed-competent misfolded tau species do not acutely cause cell death, but instead initiate discrete cellular dysfunctions.
0270-6474
9623-9632
Hallinan, Grace
5549f978-4afd-4b1c-a4e1-6fe6530d3573
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1
Hallinan, Grace
5549f978-4afd-4b1c-a4e1-6fe6530d3573
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
West, Jonathan
f1c2e060-16c3-44c0-af70-242a1c58b968
Deinhardt, Katrin
5f4fe23b-2317-499f-ba6d-e639a4885dc1

Hallinan, Grace, Vargas-Caballero, Mariana, West, Jonathan and Deinhardt, Katrin (2019) Tau misfolding efficiently propagates between individual intact hippocampal neurons. The Journal of Neuroscience, 39 (48), 9623-9632. (doi:10.1523/JNEUROSCI.1590-19.2019).

Record type: Article

Abstract

Neurofibrillary tangles, formed of misfolded, hyperphosphorylated tau protein, are a pathological hallmark of several neurodegenerations, including Alzheimer's disease. Tau pathology spreads between neurons and propagates misfolding in a prion-like manner throughout connected neuronal circuits. Tauopathy is accompanied by significant neuronal death, but the relationships between initial tau misfolding, propagation across connected neurons and cytotoxicity remain unclear. In particular the immediate functional consequence of tau misfolding for the individual neuron is not well understood. Here, using microfluidic devices to recreate discretely organized neuronal connections, we show that the spread and propagation of misfolded tau between individual murine neurons is rapid and efficient; it occurs within days. The neurons containing and propagating tau pathology display selective axonal transport deficits but remain viable and electrically competent. Therefore, we demonstrate that seed-competent misfolded tau species do not acutely cause cell death, but instead initiate discrete cellular dysfunctions.

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2019 Hallinan - Accepted Manuscript
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Accepted/In Press date: 1 October 2019
e-pub ahead of print date: 28 October 2019
Published date: 27 November 2019

Identifiers

Local EPrints ID: 434944
URI: http://eprints.soton.ac.uk/id/eprint/434944
ISSN: 0270-6474
PURE UUID: 159f62d0-d045-4b1f-8845-bbc48fa1d565
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001
ORCID for Jonathan West: ORCID iD orcid.org/0000-0002-5709-6790
ORCID for Katrin Deinhardt: ORCID iD orcid.org/0000-0002-6473-5298

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Date deposited: 16 Oct 2019 16:30
Last modified: 22 Nov 2021 07:44

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Contributors

Author: Grace Hallinan
Author: Jonathan West ORCID iD

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