 In patients with Alzheimer's disease, the gradual decline in cognitive function and loss of neurons is preceded by the harmful buildup of the protein tau in the brain. Tau initially accumulates as toxic clusters called aggregates in brain regions that are critical for learning and memory. But how these toxic tau aggregates spread during the early stage of Alzheimer's was unknown until recently. This study found that tau aggregates can be carried from one neuron to another by the brain's own immune cells in a process that may contribute to the progression of Alzheimer's disease. One important function of the brain's immune cells, called microglia, is to constantly search brain tissue for materials that might indicate injury or infection. For this purpose, microglia actively engulf dead cells, debris, and even unhealthy living synapses or entire neurons. Then, microglia release membrane-bound spheres called exosomes, which can be taken up by other cells. This process enables microglia to present potentially infectious material to the immune system to activate an immune response. The authors of this study hypothesized that in a patient with Alzheimer's disease, microglia might actually help spread the harmful protein tau by taking up tau-containing synapses and then releasing tau via exosomes, which are then absorbed by nearby neurons. To test this hypothesis, mice were injected with a non-replicating virus modified to produce human tau only in neurons. The injections were made into the entorhinal cortex, the location where tau aggregates originate in Alzheimer's disease patients even before the onset of symptoms. One week after the virus was injected, human tau expression was detected only in the entorhinal cortex, but after four weeks it was also detected in the hippocampus. The spread of tau aggregates to the hippocampus is clinically important because this event is often associated with memory lapses, a hallmark of early Alzheimer's disease. In these mice, tau was found predominantly in neurons and, to a lesser extent, in microglia. The accumulation of tau in hippocampal neurons hindered their ability to function in the neural network. However, depleting microglia from the brain markedly suppressed the spread of tau to hippocampal neurons and preserved the function of these cells. Specifically blocking the formation of exosomes also prevented tau from accumulating in the hippocampus. In addition, using a common animal model of Alzheimer's disease in which the mice have been genetically modified to express human tau protein in the brain, the authors confirmed that blocking exosome function suppressed the spread of tau in the brain. Taken together, these results suggest that during the early stage of Alzheimer's disease, microglia facilitate the spread of tau aggregates between neurons by releasing tau-containing exosomes. This finding indicates that factors involved in exosome release by microglia might be used as novel therapeutic agents to prevent the progression of Alzheimer's disease.