Shah, D;
Gsell, W;
Wahis, J;
Luckett, ES;
Jamoulle, T;
Vermaercke, B;
Preman, P;
... De Strooper, B; + view all
(2022)
Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease.
Cell Reports
, 40
(8)
, Article 111280. 10.1016/j.celrep.2022.111280.
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Abstract
Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex several years before amyloid deposition. We find the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astrocytic calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral disruptions. In conclusion, we show that astrocytes mediate initial features of AD and drive clinically relevant phenotypes.
| Type: | Article |
|---|---|
| Title: | Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2022.111280 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2022.111280 |
| Language: | English |
| Additional information: | © 2022 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
| Keywords: | App mice, BOLD rsfMRI, CP: Neuroscience, amyloid pathology, astrocytes, calcium signaling, neuronal hyperactivity, Alzheimer Disease, Amyloid beta-Peptides, Animals, Astrocytes, Calcium, Calcium Signaling, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Neurons |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10155083 |
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