Using Astrocyte Factors to Prevent Synaptic Alterations in Alzheimer’s Disease

The brain is the center of command of our bodies, controlling our motion, our behavior and our feelings. Its main components, the neurons, process information by making specialized connections (synapses) between them assisted by other important types of cells: the astrocytes. Alzheimer’s disease is associated with alterations in these connections. In this project I aim to restore the correct function of astrocytes, to rescue synaptic defects, in mouse models affected by Alzheimer disease and make a step further to the cure of this devastating disorder.

The brain is the center of command of our bodies. It controls our motion, our behavior, our feelings, our memories. Its main components, the neurons, process information by making fast connections, synapses, with each other. They are assisted by another important set of cells: the astrocytes. Astrocytes are cells with a star-shape that can contact more than one thousand different synapses. Their presence at the synapse is essential for correct transmission of information. In Alzheimer’s disease these synapses are lost, but we still do not fully understand why and how. In this project, I will study if changes to astrocytes in Alzheimer’s disease are responsible for the loss of synapses. To study this, I am using mice that have mutations in genes associated with Alzheimer’s disease, and that develop symptoms of the disease. Using these mice, I found that in Alzheimer’s disease astrocytes produce more levels of a factor, Glypican 5, important for synaptic function. I will test if this increase in Glypican 5 is toxic for synapses and is contributing to their loss in Alzheimer’s disease. I will do this by decreasing the levels of Glypican 5 in astrocytes from mice affected by Alzheimer’s disease. I expect that this reduction will restore the correct function of the synapses. These discoveries may have important implications for Alzheimer’s disease, by identifying a new way to prevent synapse loss and take a step further to the cure of this devastating disease.