PROJECT SUMMARY Alzheimer’s disease (AD) is a late-onset neurodegenerative disease marked by a progressive loss of memory and other cognitive functions, resulting in profound dementia. AD is the most common late-onset dementia affecting millions of people in the developed countries of the world and the AD population predicted to reach 130 million by 2050. There has been a concerted effort to identify the mechanism of disease, development of models and therapeutics. In AD and other neurodegenerative diseases, the observations of uncontrolled chronic inflammatory pathology in the CNS and genetic associations of immune pathways have implicated the microglia. The microglia are the key immune cells in the CNS which provide immunesurveillance, secrete inflammatory molecules, and clear cell debris from the extracellular space. In AD, there is an uncoupling of microglial activation and phagocytosis functions suggesting that these cells are targets for AD drug discovery. Recently, human iPS-derived microglia (iMGLs) models have started to become available. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize an in vitro high throughput, high content functional suite of AD iMGLs assays with the Phenovista’s proprietary culture screening system. These assays will allow for a next-generation in vitro system for ranking the relative efficacy of AD microglial based therapies.