Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease

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State: Public
Version: Author's accepted manuscript
License: CC BY 4.0
Serval ID
serval:BIB_7B4EC9A90D9A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer’s disease
Journal
Nature Neuroscience
Author(s)
Richetin Kevin, Steullet Pascal, Pachoud Mathieu, Perbet Romain, Parietti Enea, Maheswaran Mathischan, Eddarkaoui Sabiha, Bégard Séverine, Pythoud Catherine, Rey Maria, Caillierez Raphaelle, Do Kim, Halliez Sophie, Bezzi Paola, Buée Luc, Leuba Geneviève, Colin Morvane, Toni Nicolas, Déglon Nicole
Publication state
Published
Issued date
09/11/2020
Volume
23
Pages
1567–1579
Language
english
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.
Create date
08/10/2020 18:02
Last modification date
26/02/2021 7:25
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