MICROGLIAL STRUCTURAL SIMPLIFICATION AROUND AMYLOID PLAQUES LINKED TO MEMBRANE LOSS IN AN ALZHEIMER’S DISEASE MOUSE MODEL

Microglia are specialized cells in the central nervous system that have functional similarity to macrophages, cleaning up cellular byproducts and debris. When they are in their homeostatic state, they surveil their surroundings by spreading their processes in many directions. Once they find a target that requires their attention, they migrate to that site and acquire an amoeboid shape. This process is referred to as simplification and is documented to occur around β-Amyloid plaques, a key hallmark in Alzheimer’s Disease. Also seen around these plaques are upregulated lipid droplets within microglia, indicating membrane changes. We set out to quantify the degree of change that microglial branching, surface area, and volume undergo as they change shape, investigating if membrane is lost during this process. 30 μm coronal slices were taken from 5xFAD+/- APOE4+/+ CX3CR1-GFP+/- mice and imaged to visualize microglia (genetically tagged with Green Fluorescent Protein) and Aβ plaques (stained with MOAB-2) using a Leica Mica confocal microscope. IMARIS software was used to create surface and skeletal reconstructions of microglia for surface area, volume, and branching measurements. We found that with decreased branching, surface area significantly decreases by a factor of two on average, while volume does not significantly change. We also confirmed that microglia have less surface area and branching complexity near plaques. We concluded that microglia going through the process of simplification lose membrane, with this process reliably occurring near AB plaques as well. We infer that this process is intrinsically linked to the formation of lipid droplets.