Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease
- 9 November 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 23 (12), 1567-1579
- https://doi.org/10.1038/s41593-020-00728-x
Abstract
Alzheimer’s disease (AD) is characterized by the accumulation of the tau protein in neurons, neurodegeneration and memory loss. However, the role of non-neuronal cells in this chain of events remains unclear. In the present study, we found accumulation of tau in hilar astrocytes of the dentate gyrus of individuals with AD. In mice, the overexpression of 3R tau specifically in hilar astrocytes of the dentate gyrus altered mitochondrial dynamics and function. In turn, these changes led to a reduction of adult neurogenesis, parvalbumin-expressing neurons, inhibitory synapses and hilar gamma oscillations, which were accompanied by impaired spatial memory performances. Together, these results indicate that the loss of tau homeostasis in hilar astrocytes of the dentate gyrus is sufficient to induce AD-like symptoms, through the impairment of the neuronal network. These results are important for our understanding of disease mechanisms and underline the crucial role of astrocytes in hippocampal function.Funding Information
- Stiftung Synapsis - Alzheimer Forschung Schweiz AFS
This publication has 77 references indexed in Scilit:
- Ca2+ Regulation of Mitochondrial ATP Synthesis Visualized at the Single Cell LevelACS Chemical Biology, 2011
- Three Repeat Isoforms of Tau Inhibit Assembly of Four Repeat Tau FilamentsPLOS ONE, 2010
- Immunohistochemical detection of transgene expression in the brain using small epitope tagsBMC Biotechnology, 2010
- Driving fast-spiking cells induces gamma rhythm and controls sensory responsesNature, 2009
- Differential Regulation of Dynein and Kinesin Motor Proteins by TauScience, 2008
- GFAP promoter elements required for region‐specific and astrocyte‐specific expressionGlia, 2008
- Single molecule profiling of tau gene expression in Alzheimer’s diseaseJournal of Neurochemistry, 2007
- Expression of tau mRNA and soluble tau isoforms in affected and non‐affected brain areas in Alzheimer's diseaseFEBS Letters, 2004
- Structural and Functional Differences between 3-Repeat and 4-Repeat Tau IsoformsOnline Journal of Public Health Informatics, 2000
- Self-Inactivating Lentiviral Vectors with Enhanced Transgene Expression as Potential Gene Transfer System in Parkinson's DiseaseHuman Gene Therapy, 2000