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.

阿尔茨海默病 (AD) 的特征是 tau 蛋白在神经元中的积累、神经退行性变和记忆丧失。然而，非神经元细胞在这一系列事件中的作用仍不清楚。在本研究中，我们发现 tau 在 AD 患者齿状回的肺门星形胶质细胞中积累。在小鼠中，3R tau 在齿状回肺门星形胶质细胞中的过度表达改变了线粒体动力学和功能。反过来，这些变化导致成人神经发生、表达小白蛋白的神经元、抑制性突触和肺门伽马振荡减少，并伴有空间记忆能力受损。总之，这些结果表明齿状回肺门星形胶质细胞中 tau 稳态的丧失足以诱发 AD 样症状，通过神经元网络的损伤。这些结果对于我们了解疾病机制很重要，并强调了星形胶质细胞在海马功能中的关键作用。