Tau Overexpression Results in Its Secretion via Membrane Vesicles

Background: Tau protein, the main component of neurofibrillary tangles, could be found in the extracellular space upon neuronal death or, as it has recently been suggested, could be secreted from cells through membrane vesicles. Objective: The purpose of this communication is to confirm that upon neuronal death, tau protein can be found, indeed, in the extracellular space and to analyze if tau could be secreted outside the cell in an alternative way. Methods: We have tested not only the extracellular release of tau, but also the toxicity of this extracellular tau. To do these studies, we have used neuronal cell cultures and tau-overexpressing non-neuronal cells. Membrane vesicles were isolated from culture medium from tau-overexpressing non-neuronal cells. Results: Our results indicate that extracellular tau, arising after neuron death, could be a toxic agent for neighboring neurons. On the other hand, we have found that an overexpression of tau protein could result in its secretion through membrane vesicles. However, the presence of this secreted tau does not result in cell death. Conclusion: We conclude that extracellular tau could arise by two different ways, by cell death or by secretion through membrane vesicles.