Alterations in the metabolism of the neuronal microtubule-associated protein tau are central to several neurodegenerative diseases. In these diseases, tau usually loses solubility and forms aggregates that impair cell function to trigger neuronal cell death and neurodegeneration. However, the in vivo neurotoxic potential of soluble tau is not yet fully understood. Bolós et al. stereotactically injected human soluble tau into the dentate gyrus of mice. Hippocampal granule neurons showed markedly reduced synapse numbers in the molecular layer. In addition, newborn granule cells showed reduced numbers of dendritic spines. Behaviorally, these animals exhibited an impaired capacity to perform pattern separation. Soluble tau thus causes long-term damage to the morphology and connectivity of newborn granule cells.
