Astrocyte Calcium Dysfunction Causes Early Network Hyperactivity in Alzheimer's Disease

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Aug 24

PMID 36001964

Authors

Disha Shah

Willy Gsell

Jerome Wahis

Emma S Luckett

Tarik Jamoulle

Ben Vermaercke

Pranav Preman

Daan Moechars

Veronique Hendrickx

Tom Jaspers

Katleen Craessaerts

Katrien Horre

Leen Wolfs

Mark Fiers

Matthew Holt

Dietmar Rudolf Thal

Zsuzsanna Callaerts-Vegh

Rudi DHooge

Rik Vandenberghe

Uwe Himmelreich

Vincent Bonin

Bart De Strooper

Affiliations

Soon will be listed here.

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 App 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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