| First Author | Shah D | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 8 | Pages | 111280 |
| PubMed ID | 36001964 | Mgi Jnum | J:328275 |
| Mgi Id | MGI:7334660 | Doi | 10.1016/j.celrep.2022.111280 |
| Citation | Shah D, et al. (2022) Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease. Cell Rep 40(8):111280 |
| abstractText | 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(NL-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. |
