Our research group has discovered that microglia play a critical role in compressing and insulating amyloid plaques. This process renders the plaques less toxic to adjacent neurons. This proposal seeks to use sophisticated live-imaging and high-resolution microscopy combined with molecular manipulations to investigate how microglia interact with astrocytes during the protective encapsulation of amyloid plaques. The hypothesis for this research is that the coordination between these two glial cells, astrocytes and microglia, is critical for preventing damage to the long, threadlike part of a nerve cell called an axon that propagates an electrical signal to the synapse. The hope is that understanding this interaction will enable a therapeutic intervention to diminish the progression of neural dysfunction in Alzheimer’s disease.