INPP5D is a human gene encoding an unusual enzyme associated with Alzheimer’s disease. The enzyme is unusual partly because it appears to control access to a part of the cell known as the lysosome, a bubble-like structure that acts as a garbage disposal, among other actions. The enzyme also is unusual because it can decorate two disparate chemicals: proteins and inositide fats. In the brain, expression of the INPP5D gene is concentrated in inflammatory cells known as microglia; therefore, we propose to use genetic engineering of mouse models to assess how microglial-specific INPP5D knockdown modulates amyloidosis, tauopathy and behavior in Alzheimer’s mouse models.
