Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease
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 unk...
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| Veröffentlicht in: | CELL REPORTS 2022-08, Vol.40 (8) |
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| creator | Shah, Disha Gsell, Willy Wahis, Jerome Luckett, Emma S Jamoulle, Tarik Vermaercke, Ben Preman, Pranav Moechars, Daan Hendrickx, Veronique Jaspers, Tom Craessaerts, Katleen Horre, Katrien Wolfs, Leen Fiers, Mark Holt, Matthew Thal, Dietmar Rudolf Callaerts-Vegh, Zsuzsanna D'Hooge, Rudi Vandenberghe, Rik Himmelreich, Uwe Bonin, Vincent De Strooper, Bart |
| description | 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. |
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| title | Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease |
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