Microphysiological systems to Advance Precision medicine for Alzheimer's Disease and Related Dementias (MAP-AD)

PROJECT ABSTRACT/SUMMARY IU MAP-AD Overall Abstract/Summary The Indiana University Microphysiological systems to Advance Precision medicine for AD/ADRD (IUMAP-AD) Center is committed to establishing a multi-component Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD) Translational Center for Microphysiological Systems (MPS). AD is a leading cause of dementia worldwide, with current estimates of nearly 6 million Americans currently affected by the disease. AD is associated with many accompanying pathologies including inflammation and activation of microglia and astrocytes, dysfunction of vasculature, as well as synaptic and eventual neuronal loss. Additionally, recent studies have identified numerous genetic risk factors associated with AD/ADRD at loci with known functions in glial and vascular cell types. However, our understanding of how these genetic risk factors and cell types contribute to AD/ADRD pathology remains somewhat limited, especially in the human system. Thus, to overcome these shortcomings, we propose to build on our extensive knowledge and tools acquired from the ongoing MODEL-AD, TREAT-AD, and CLEAR-AD consortia at Indiana University, as well as our extensive expertise in induced pluripotent stem cell (iPSC)/organoids, intelligent systems, and AD/ADRD research across the University. Our overarching goal is to develop reproducible, scalable, and standardized 3D brain organoid-based MPS models that recapitulate key features of human AD/ADRD pathophysiology. In the process, we will also generate numerous resources for investigation among the research community which will be readily shared, including novel cell lines, protocols for the development and implementation of MPS models, and datasets derived from the use of MPS models. These models will thus serve as precision medicine research tools to investigate the complex biology of AD/ADRD and accelerate multiple aspects of drug discovery and preclinical drug development.